Histochemical and molecular overview of the thymus as site for T-cells development

Progress in Histochemistry and Cytochemistry

Volumn 43, Issue 2, 2008, Pages 73-120

  Rezzani, Rita ^a   Bonomini, Francesca ^a   Rodella, Luigi Fabrizio ^a  

^a Anatomy Section   (Italy)

Author keywords

Bone morphogenic proteins; Notch pathway; Rodents; Thymic involution; Thymic microenvironment; Thymus

Indexed keywords

CHEMOKINE; CYTOKINE; KERATINOCYTE GROWTH FACTOR; SEX HORMONE;

AGING; ARTICLE; B LYMPHOCYTE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL MATURATION; CELL MIGRATION; EMBRYO DEVELOPMENT; EPITHELIUM CELL; HORMONE SYNTHESIS; HUMAN; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; LYMPHOPOIESIS; MOLECULAR DYNAMICS; NATURAL KILLER T CELL; NEUROENDOCRINE SYSTEM; NONHUMAN; ORGANOGENESIS; PERINATAL DEVELOPMENT; PHENOTYPE; REGULATORY T LYMPHOCYTE; STROMA CELL; T LYMPHOCYTE; THYMOCYTE; THYMUS ATROPHY;

ANIMALS; HISTORY, 19TH CENTURY; HUMANS; T-LYMPHOCYTES; THYMUS GLAND;

RODENTIA;

EID: 44949128849     PISSN: 00796336     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.proghi.2008.03.001     Document Type: Article

References (220)

1. Abo T. Extrathymic pathways of T-cell differentiation and immunomodulation. Int Immunopharmacol 1 (2001) 1261-1273
2. Adkins B., and Hamilton K. Developmental ages of the thymic epithelium and of the T cell precursors together determine the proportions of peripheral CD4+ cells. J Immunol 153 (1994) 5359-5365
3. Aguilar L.K., Aguilar-Cordova E., Cartwright Jr. J., and Belmont J.W. Thymic nurse cells are sites of thymocyte apoptosis. J Immunol 152 (1994) 2645-2651
4. Alves L.A., Campos de Carvalho A.C., Cirne Lima E.O., Rocha e Souza C.M., Dardenne M., Spray D.C., et al. Functional gap junctions in thymic epithelial cells are formed by connexin 43. Eur J Immunol 25 (1995) 431-437
5. Anderson G., Moore N.C., Owen J.J., and Jenkinson E.J. Cellular interactions in thymocyte development. Annu Rev Immunol 14 (1996) 73-99
6. Anderson M., Anderson S.K., and Farr A.G. Thymic vasculature: organizer of the medullary epithelial compartment?. Int Immunol 12 (2000) 1105-1110
7. Anderson G., Lane P.J., and Jenkinson E.J. Generating intrathymic microenvironments to establish T-cell tolerance. Nat Rev Immunol 7 (2007) 954-963
8. Andrades J.A., Han B., Becerra J., Sorgente N., Hall F.L., and Nimni M.E. A recombinant human TGF-beta1 fusion protein with collagen-binding domain promotes migration, growth, and differentiation of bone marrow mesenchymal cells. Exp Cell Res 250 (1999) 485-498
9. Andrew D., and Aspinall R. Age-associated thymic atrophy is linked to a decline in IL-7 production. Exp Gerontol 37 (2002) 455-463
10. Anonymous. Medical dictionary. 29th ed (1971), Adam Black, London
11. Ara T., Itoi M., Kawabata K., Egawa T., Tokoyoda K., Sugiyama T., et al. A role of CXC chemokine ligand 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its receptor CXCR4 in fetal and adult T cell development in vivo. J Immunol 170 (2003) 4649-4655
12. Ariizumi T., and Asashima M. In vitro induction systems for analyses of amphibian organogenesis and body patterning. Int J Dev Biol 45 (2001) 273-279
13. Aspinall R. Age-associated thymic atrophy in the mouse is due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development. J Immunol 158 (1997) 3037-3045
14. Aspinall R., Andrew D., and Pido-Lopez J. Age-associated changes in thymopoiesis. Springer Semin Immunopathol 24 (2002) 87-101
15. Balciunaite G., Keller M.P., Balciunaite E., Piali L., Zuklys S., Mathieu Y.D., et al. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat Immunol 3 (2002) 1102-1108
16. Barrat F.J., Cua D.J., Boonstra A., Richards D.F., Crain C., Savelkoul H.F., et al. In vitro generation of interleukin-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (TH1)- and TH2-inducing cytokines. J Exp Med 195 (2002) 603-616
17. Beard J. The source of leucocytes and the true function of the thymus. Anat Anz 18 (1900) 550-573
18. Beelen R.H.J., Fluitsma D.M., and Hoefsmit E.C.M. Milky spots in the omentum. Cellular composition of milky spots and fine structures of milky spot macrophages and reticulum cells. J Reticuloendothel Soc 28 (1980) 585-599
19. Belkaid Y., Piccirillo C.A., Mendez S., Shevach E.M., and Sacks D.L. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420 (2002) 502-507
20. Bennett A.R., Farley A., Blair N.F., Gordon J., Sharp L., and Blackburn C.C. Identification and characterization of thymic epithelial progenitor cells. Immunity 16 (2002) 803-814
21. Benz C., Heinzel K., and Bleul C.C. Homing of immature thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development. Eur J Immunol 34 (2004) 3652-3663
22. Benz C., and Bleul C.C. A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J Exp Med 202 (2005) 21-31
23. Berg L.J. Signalling through TEC kinases regulates conventional versus innate CD8 T-cell development. Nat Rev Immunol 7 (2007) 479-485
24. Billingham R.E., Brent L., and Medawar P.B. Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance. Philos Trans R Soc London 239B (1956) 357-412
25. Billingham R.E., Defendi V., Silvers W.K., and Steinmuller D.J. Quantitative studies on the induction of tolerance of skin homografts and on runt disease in neonatal rats. J Nat Cancer Inst 28 (1962) 365-435
26. Blackburn C.C., and Manley N.R. Developing a new paradigm for thymus organogenesis. Nat Rev Immunol 4 (2004) 278-289
27. Blau J.N. A phagocytic function of Hassall's corpuscles. Nature 208 (1965) 564-567
28. Bleul C.C., and Boehm T. BMP signaling is required for normal thymus development. J Immunol 175 (2005) 5213-5221
29. Bluestone J.A., and Abbas A.K. Natural versus adaptive regulatory T cells. Nat Rev Immunol 3 (2003) 253-257
30. Bockman D.E. Development of the thymus. Microsc Res Techn 38 (1997) 209-215
31. Bodey B., Bodey Jr. B., Siegel S.E., and Kaiser H.E. Novel insights into the function of the thymic Hassall's bodies. In Vivo 14 (2000) 407-418
32. Boehm T., Scheu S., Pfeffer K., and Bleul C.C. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. J Exp Med 198 (2003) 757-769
33. Bolotin E., Smogorzewska M., Smith S., Widmer M., and Weinberg K. Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood 88 (1996) 1887-1894
34. Boyd R.L., Tucek C.L., Godfrey D.I., Izon D.J., Wilson T.J., Davidson N.J., et al. The thymic microenvironment. Immunol Today 14 (1993) 445-459
35. Bray S.J. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7 (2006) 678-689
36. Brelińska R. Thymic epithelial cells in age-dependent involution. Microsc Res Techn 62 (2003) 488-500
37. Brelińska R., and Warchol J.B. Thymic nurse cells: their functional ultrastructure. Microsc Res Techn 38 (1997) 250-266
38. Cabarrocas J., Cassan C., Magnusson F., Piaggio E., Mars L., Derbinski J., et al. Foxp3+ CD25+ regulatory T cells specific for a neo-self-antigen developed at the double-positive thymic stage. Proc Natl Acad Sci USA 103 (2006) 8453-8458
39. Capdevila J., and Izpisua Belmonte J.C. Patterning mechanisms controlling vertebrate limb development. Annu Rev Cell Dev Biol 17 (2001) 87-132
40. Carballada R., Yasuo H., and Lemaire P. Phosphatidylinositol-3 kinase acts in parallel to the ERK MAP kinase in the FGF pathway during Xenopus mesoderm induction. Development 128 (2001) 35-44
41. Chen P., Carrington J.L., Hammonds R.G., and Reddi A.H. Stimulation of chondrogenesis in limb bud mesoderm cells by recombinant human bone morphogenetic protein 2B (BMP-2B) and modulation by transforming growth factor beta 1 and beta 2. Exp Cell Res 195 (1991) 509-515
42. Ciofani M., and Zúñiga-Pflücker J.C. The thymus as an inductive site for T lymphopoiesis. Annu Rev Cell Dev Biol 23 (2007) 463-493
43. Clegg C.H., Rulffes J.T., Wallace P.M., and Haugen H.S. Regulation of an extrathymic T-cell development pathway by oncostatin M. Nature 384 (1996) 261-263
44. Cooper A.P. The anatomy of the thymus gland (1832), Longmand, Rees, Orme, Green & Brown, London p. 1-48
45. Cordier A.C., and Haumond S.M. Development of thymus, parathyroids, and ultimobranchial bodies in NMRI and nude mice. Am J Anat 157 (1980) 227-254
46. Crotti A. The thymus gland. In: Crotti A. (Ed). Thyroid and thymus (1922), Lea & Febiger, Philadelphia 607-693
47. Dale T.C. Signal transduction by the Wnt family of ligands. Biochem J 329 (1998) 209-223
48. Dally A. Status lymphaticus: sudden death in children from "visitation of God" to cot death. Med History 41 (1997) 70-85
49. Damoiseaux J.G., Cautain B., Bernard I., Mas M., van Breda Vriesman P.J., Druet P., et al. A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8T cell ratio in the rat. J Immunol 163 (1999) 2983-2989
50. Dardenne M., and Savino W. Control of thymus physiology by peptidic hormones and neuropeptides. Immunol Today 15 (1994) 518-523
51. Dardenne M., Savino W., Gagnerault M.C., Itoh T., and Bach J.F. Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells. Endocrinology 125 (1989) 3-12
52. De Waal E.J., and Rademakers L.H. Heterogeneity of epithelial cells in the rat thymus. Microsc Res Techn 38 (1997) 227-236
53. Deftos M.L., Huang E., Ojala E.W., Forbush K.A., and Bevan M.J. Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes. Immunity 13 (2000) 73-84
54. Derbinski J., Gäbler J., Brors B., Tierling S., Jonnakuty S., Hergenhahn M., et al. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med 202 (2005) 33-45
55. Derynck R., Akhurst R.J., and Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29 (2001) 117-129
56. Dieckmann D., Bruett C.H., Ploettner H., Lutz M.B., and Schuler G. Human CD4+CD25+ regulatory, contact-dependent T cells induce interleukin-10-producing, contact-independent type-1-like regulatory T cells. J Exp Med 196 (2002) 247-253
57. Dietrich S., and Gruss P. Undulated phenotypes suggest a role of Pax-1 for the development of vertebral and extravertebral structures. Dev Biol 167 (1995) 529-548
58. Dipasquale B., and Tridente G. Immunohistochemical characterization of nurse cells in normal human thymus. Histochemistry 96 (1991) 499-503
59. Domínguez-Gerpe L., and Rey-Méndez M. Evolution of the thymus size in response to physiological and random events throughout life. Microsc Res Techn 62 (2003) 464-476
60. Doyle D. William Hewson (1739-74): the father of haematology. Br J Haematol 133 (2006) 375-381
61. Dudgeon L.S.L. A contribution to the pathology of the thymus gland. Trans Path Soc Lond 55 (1904) 151-203
62. Duijvestijn A.M., and Hoefsmit E.C.M. Ultrastructure of the rat thymus: the micro-environment of T-lymphocyte maturation. Cell Tissue Res 218 (1981) 279-292
63. Dupé V., Ghyselinck N.B., Wendling O., Chambon P., and Mark M. Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse. Development 126 (1999) 5051-5059
64. Eldar A., Dorfman R., Weiss D., Ashe H., Shilo B.Z., and Barkai N. Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 419 (2002) 304-308
65. Erickson M., Morkowski S., Lehar S., Gillard G., Beers C., Dooley J., et al. Regulation of thymic epithelium by keratinocyte growth factor. Blood 100 (2002) 3269-3278
66. Fagge C.H. Textbook of the principles and practice of medicine (1886), J & A Churchill, London p. 784
67. Farr A.G., Hosier S., Braddy S.C., Anderson S.K., Eisenhardt D.J., Yan Z.J., et al. Medullary epithelial cell lines from murine thymus constitutively secrete IL-1 and hematopoietic growth factors and express class II antigens in response to recombinant interferon-gamma. Cell Immunol 119 (1989) 427-433
68. Farr A.G., Dooley J.L., and Erickson M. Organization of thymic medullary epithelial heterogeneity: implications for mechanisms of epithelial differentiation. Immunol Rev 189 (2002) 20-27
69. Felten D.F., Felten S.Y., Carlson S.L., Olschowka J.A., and Livnat S. Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 135 (1985) 755s-765s
70. Fontenot J.D., and Rudensky A. A well adapted regulatory contrivance: regulatory T-cell development and the forkhead family transcription factor family Foxp3. Nat Immunol 6 (2005) 331-337
71. Fry T.J., and Mackall C.L. Current concepts of thymic aging. Springer Semin Immunopathol 24 (2002) 7-22
72. Furtado G.C., de Lafaille M.A., Kutchukhidze N., and Lafaille J.J. Interleukin-2 signaling is required for CD4+ regulatory T-cell function. J Exp Med 196 (2002) 851-857
73. Gapin L., Matsuda J.L., Surh C.D., and Kronenberg M. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat Immunol 2 (2001) 971-978
74. García-Suárez O., Pérez-Pérez M., Germanà A., Esteban I., and Germanà G. Involvement of growth factors in thymic involution. Microsc Res Techn 62 (2003) 514-523
75. Garg V., Yamagishi C., Hu T., Kathiriya I.S., Yamagishi H., and Srivastava D. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Dev Biol 235 (2001) 62-73
76. Gill J., Malin M., Hollander G.A., and Boyd R. Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat Immunol 3 (2002) 635-642
77. Gill J., Malin M., Sutherland J., Gray D., Hollander G., and Boyd R. Thymic generation and regeneration. Immunol Rev 195 (2003) 28-50
78. Goldman K.P., Park C.S., Kim M., Matzinger P., and Anderson C.C. Thymic cortical epithelium induces self-tolerance. Eur J Immunol 35 (2005) 709-717
79. Gonzalez A., Andre-Schmutz I., Carnaud C., Mathis D., and Benoist C. Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes. Nat Immunol 2 (2001) 1117-1125
80. Gowans J.L., Gesner B.M., and McGregor D.D. The immunological activity of lymphocytes. In: Wolstenholme G.E.W., and O'Connor M. (Eds). Biological activity of the leucocyte (1961), Churchill, London 32-44
81. Graf D., Nethisinghe S., Palmer D.B., Fisher A.G., and Merkenschlager M. The developmentally regulated expression of Twisted gastrulation reveals a role for bone morphogenetic proteins in the control of T cell development. J Exp Med 196 (2002) 163-171
82. Gray D.H., Ueno T., Chidgey A.P., Malin M., Goldberg G.L., Takahama Y., et al. Controlling the thymic microenvironment. Curr Opin Immunol 17 (2005) 137-143
83. Gray D.H., Seach N., Ueno T., Milton M.K., Liston A., Lew A.M., et al. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108 (2006) 3777-3785
84. Gruver A.L., Hudson L.L., and Sempowski G.D. Immunosenescence of ageing. J Pathol 211 (2007) 144-156
85. Guidos C. Thymus and T-lymphocyte development: what is new in the 21st century?. Immunol Rev 209 (2006) 5-9
86. Guidos C.J., Weissman I.L., and Adkins B. Developmental potential of CD4-8- thymocytes. Peripheral progeny include mature CD4-8- T cells bearing alpha beta T cell receptor. J Immunol 142 (1989) 3773-3780
87. Gulliver G. The works of William Hewson, FRS (1846), Sydenham Society, London
88. Guntheroth W.G. The thymus, suffocation, and sudden infant death syndrome: social agenda or hubris?. Perspect Biol Med 37 (1993) 2-13
89. Hager-Theodorides A.L., Outram S.V., Shah D.K., Sacedon R., Shrimpton R.E., Vicente A., et al. Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol 169 (2002) 5496-5504
90. Haley P.J. Species differences in the structure and function of the immune system. Toxicology 188 (2003) 49-71
91. Han H., Tanigaki K., Yamamoto N., Kuroda K., Yoshimoto M., Nakahata T., et al. Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int Immunol 14 (2002) 637-645
92. Hartwig M., and Steinmann G. On a causal mechanism of chronic thymic involution in man. Mec Ageing Dev 75 (1994) 151-156
93. Haynes B.F., Markert M.L., Sempowski G.D., Patel D.D., and Hale L.P. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol 18 (2000) 529-560
94. He W., Zhang Y., Deng Y., and Kabelitz D. Induction of TCR-gd expression on triple-negative (CD324282) human thymocytes. Comparative analysis of the effects of IL-4 and IL-7. J Immunol 154 (1995) 3726-3731
95. Henson S.M., Pido-Lopez J., and Aspinall R. Reversal of thymic atrophy. Exp Gerontol 39 (2004) 673-678
96. Huelsken J., and Birchmeier W. New aspects of Wnt signaling pathways in higher vertebrates. Curr Opin Genet Dev 11 (2001) 547-553
97. Huelsken J., Vogel R., Erdmann B., Cotsarelis G., and Birchmeier W. Beta-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105 (2001) 533-545
98. Ikawa T., Kawamoto H., Goldrath A.W., and Murre C. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 203 (2006) 1329-1342
99. Itoi M., Kawamoto H., Katsura Y., and Amagai T. Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. Int Immunol 13 (2001) 1203-1211
100. Jameson S.C., Hogquist K.A., and Bevan M.J. Positive selection of thymocytes. Ann Rev Immunol 13 (1995) 93-126
101. Jenkinson W.E., Jenkinson E., and Anderson G. Differential requirement for mesenchyme in the proliferation and maturation of thymic epithelial progenitors. J Exp Med 198 (2003) 325-332
102. Jimenez E., Vicente A., Sacedon R., Munoz J.J., Weinmaster G., Zapata A.G., et al. Distinct mechanisms contribute to generate and change the CD4:CD8 cell ratio during thymus development: a role for the Notch ligand, Jagged1. J Immunol 166 (2001) 5898-5908
103. Jordan M.S., Boesteanu A., Reed A.J., Petrone A.L., Holenbeck A.E., Lerman M.A., et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2 (2001) 301-306
104. Jotereau F., Heuze F., Salomon-Vie V., and Gascan H. Cell kinetics in the fetal mouse thymus: precursor cell input, proliferation, and emigration. J Immunol 138 (1987) 1026-1030
105. Kaneshima H., Ito M., Asai J., Taguchi O., and Hiai H. Thymic epithelial reticular cell subpopulations in mice defined by monoclonal antibodies. Lab Invest 56 (1987) 372-380
106. Kaneta M., Osawa M., Sudo K., Nakauchi H., Farr A.G., and Takahama Y. A role for pref-1 and HES-1 in thymocyte development. J Immunol 164 (2000) 256-264
107. Kato S. Thymic microvascular system. Microsc Res Techn 38 (1997) 287-299
108. Kendall M.D. Functional anatomy of the thymic microenvironment. J Anat 177 (1991) 1-29
109. Klein L., and Kyewski B. "Promiscuous" expression of tissue antigens in the thymus: a key to T-cell tolerance and autoimmunity?. J Mol Med 78 (2000) 483-494
110. Klug D.B., Carter C., Gimenez-Conti I.B., and Richie E.R. Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus. J Immunol 169 (2002) 2842-2845
111. Kopp J.H. Denkwürdigkeiten in den är Praxis (1830), JC Hermann, Frankfurt
112. Kwan J., and Killeen N. CCR7 directs the migration of thymocytes into the thymic medulla. J Immunol 172 (2004) 3999-4007
113. Lambolez F., Azogui O., Joret A.M., Garcia C., von Boehmer H., Di Santo J., et al. Characterization of T cell differentiation in the murine gut. J Exp Med 195 (2002) 437-449
114. Lannes-Vieira J., Dardenne M., and Savino W. Extracellular matrix components of the mouse thymus microenvironment: ontogenetic studies and modulation by glucocorticoid hormones. J Histochem Cytochem 39 (1991) 1539-1546
115. Le Douarin N.M., and Jotereau F.V. Tracing of cells of the avian thymus through embryonic life in interspecific chimeras. J Exp Med 142 (1975) 17-40
116. Leveen P., Carlsen M., Makowska A., Oddsson S., Larsson J., Goumans M.J., et al. TGF-beta type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo. Blood 106 (2005) 4234-4240
117. Li L., Hsu H.C., Stockard C.R., Yang P., Zhou J., Wu Q., et al. IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte proliferation. J Immunol 172 (2004) 2909-2916
118. Licona P., Chimal-Monroy J., and Soldevila G. Inhibins are the major activin ligands expressed during early thymocyte development. Dev Dyn 235 (2006) 1124-1132
119. Licona-Limón P., and Soldevila G. The role of TGF-beta superfamily during T cell development: new insights. Immunol Lett 109 (2007) 1-12
120. Lind E.F., Prockop S.E., Porritt H.E., and Petrie H.T. Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development. J Exp Med 194 (2001) 127
121. Lindsay E.A., Vitelli F., Su H., Morishima M., Huynh T., Pramparo T., et al. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 410 (2001) 97-101
122. Liu C., Ueno T., Kuse S., Saito F., Nitta T., Piali L., et al. The role of CCL21 in recruitment of T-precursor cells to fetal thymi. Blood 105 (2005) 31-39
123. Lucas P.J., Kim S.J., Melby S.J., and Gress R.E. Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor. J Exp Med 191 (2000) 1187-1196
124. MacLean L.D., Zak S.J., Varco R.L., and Good R.A. The role of the thymus in antibody production: an experimental study of the immune response in thymectomized rabbits. Transplant Bull 4 (1956) 21-22
125. Maeshima A., Nojima Y., and Kojima I. The role of the activin-follistatin system in the developmental and regeneration processes of the kidney. Cytokine Growth Factor Rev 12 (2001) 289-298
126. Maloy K.J., and Powrie F. Regulatory T cells in the control of immune pathology. Nat Immunol 2 (2001) 816-822
127. Manley N.R., and Capecchi M.R. The role of Hoxa-3 in mouse thymus and thyroid development. Development 121 (1995) 1989-2003
128. Marchetti B., Guarcello V., Morale M.C., Bartoloni G., Raiti F., Palombo G., et al. Luteinizing hormone-releasing hormone (LHRH) agonist restoration of age-associated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity. Endocrinology 125 (1989) 1037-1045
129. Matloubian M., Lo C.G., Cinamon G., Lesneski M.J., Xu Y., Brinkmann V., et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427 (2004) 355-360
130. May M.T. Galen on the usefulness of the parts of the body (1968), Cornell University Press, Ithaca, New York p. 30
131. Mello-Coelho V., Villa-Verde D.M., Dardenne M., and Savino W. Pituitary hormones modulate cell-cell interactions between thymocytes and thymic epithelial cells. J Neuroimmunol 76 (1997) 39-49
132. Merscher S., Funke B., Epstein J.A., Heyer J., Puech A., Lu M.M., et al. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104 (2001) 619-629
133. Miller J.F. Analysis of the thymus influence in leukaemogenesis. Nature 191 (1961) 248-249
134. Miller J.F. The discovery of thymus function and of thymus-derived lymphocytes. Immunol Rev 185 (2002) 7-14
135. Min D., Taylor P.A., Panoskaltsis-Mortari A., Chung B., Danilenko D.M., Farrell C., et al. Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation. Blood 99 (2002) 4592-4600
136. Misslitz A., Pabst O., Hintzen G., Ohl L., Kremmer E., Petrie H.T., et al. Thymic T cell development and progenitor localization depend on CCR7. J Exp Med 200 (2004) 481-491
137. Moustakas A., Pardali K., Gaal A., and Heldin C.H. Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol Lett 82 (2002) 85-91
138. Mullor J.L., Dahmane N., Sun T., and Ruiz i Altaba A. Wnt signals are targets and mediators of Gli function. Curr Biol 11 (2001) 769-773
139. Naquet P., Naspetti M., and Boyd R.L. Development, organisation and function of the thymic medulla in normal, immunodeficient or autoimmune mice. Semin Immunol 11 (1999) 47-55
140. Nehls M., Pfeifer D., Schorpp M., Hedrich H., and Boehm T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372 (1994) 103-107
141. Nehls M., Kyewski B., Messerle M., Waldschutz R., Schuddekopf K., Smith A.J., et al. Two genetically separable steps in the differentiation of thymic epithelium. Science 272 (1996) 886-889
142. Nishino M., Ashiku S.K., Kocher O.N., Thurer R.L., Boiselle P.M., and Hatabu H. The thymus: a comprehensive review. Radiographics 26 (2006) 335-348
143. Nosaka T., Morita S., Kitamura H., Nakajima H., Shibata F., Morikawa Y., et al. Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. Mol Cell Biol 23 (2003) 2969-2980
144. Nossal G.J.V. Negative selection of lymphocytes. Cell 76 (1994) 229-239
145. Nusse R., and Varmus H.E. Wnt genes. Cell 69 (1992) 1073-1087
146. Ohlmacher A.P. Status lymphaticus. In: Buck A.H. (Ed). A reference handbook of the medical sciences embracing the entire range of scientific and practical medicine and allied science (1904), Wood, New York 446-454
147. Olsen N.J., Viselli S.M., Shults K., Stelzer G., and Kovacs W.J. Induction of immature thymocyte proliferation after castration of normal male mice. Endocrinology 134 (1994) 107-113
148. Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., and Lax I. Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci USA 98 (2001) 6074-6079
149. Oosterwegel M.A., Haks M.C., Jeffry U., Murray R., and Kruisbeek A.M. Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells. Immunity 6 (1997) 351-360
150. Ornitz D.M. FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays 22 (2000) 108-112
151. Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., et al. Receptor specificity of the fibroblast growth factor family. J Biol Chem 271 (1996) 15292-15297
152. Ortman C.L., Dittmar K.A., Witte P.L., and Le P.T. Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int Immunol 14 (2002) 813-822
153. Osada M., Ito E., Fermin H.A., Vazquez-Cintron E., Venkatesh T., Friedel R.H., et al. The Wnt signaling antagonist Kremen1 is required for development of thymic architecture. Clin Dev Immunol 13 (2006) 299-319
154. Patel D.D., and Haynes B.F. Cell adhesion molecules involved in intrathymic T cell development. Semin Immunol 5 (1993) 282-292
155. Paz P., Sanchez A., Melcon C., Fernandez J.C., and Charmorro C.A. A study of the chick thymus microenvironment during development: analysis by monoclonal antibodies against thymic epithelium. Anat Rec 235 (1993) 296-302
156. Pearse G. Normal structure, function and histology of the thymus. Toxicol Pathol 34 (2006) 504-514
157. Pecina M., Jelic M., Martinovic S., Haspl M., and Vukicevic S. Articular cartilage repair: the role of bone morphogenetic proteins. Int Orthop 26 (2002) 131-136
158. Peters H., Neubüser A., Kratochwil K., and Balling R. Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes Dev 12 (1998) 2735-2747
159. Petrie H.T., and Zúñiga-Pflücker J.C. Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol 25 (2007) 649-679
160. Plotkin J., Prockop S.E., Lepique A., and Petrie H.T. Critical role for CXCR4 signaling in progenitor localization and T cell differentiation in the postnatal thymus. J Immunol 171 (2003) 4521-4527
161. Pongracz J., Hare K., Harman B., Anderson G., and Jenkinson E.J. Thymic epithelial cells provide Wnt signals to developing thymocytes. Eur J Immunol 33 (2003) 1949-1956
162. Porritt H.E., Rumfelt L.L., Tabrizifard S., Schmitt T.M., Zúñiga-Pflücker J.C., and Petrie H.T. Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20 (2004) 735-745
163. Prockop S.E., and Petrie H.T. Regulation of thymus size by competition for stromal niches among early T cell progenitors. J Immunol 173 (2004) 1604-1611
164. Prockop S.E., Palencia S., Ryan C.M., Gordon K., Gray D., and Petrie H.T. Stromal cells provide the matrix for migration of early lymphoid progenitors through the thymic cortex. J Immunol 169 (2002) 4354-4361
165. Pui J.C., Allman D., Xu L., DeRocco S., Karnell F.G., Bakkour S., et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 11 (1999) 299-308
166. Radtke F., Wilson A., Stark G., Bauer M., van Meerwijk J., MacDonald H.R., et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10 (1999) 547-558
167. Revest J.M., Suniara R.K., Kerr K., Owen J.J., and Dickson C. Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol 167 (2001) 1954-1961
168. Rezzani R. Cyclosporine A and adverse effects on organs: histochemical studies. Prog Histochem Cytochem 39 (2004) 85-128
169. van der Rhee H.J., van der Burgh-de Winter C.P.M., and Daems W.T. The differentiation of monocytes into macrophages, epithelial cells and multinucleated giant cells in subcutaneous granulomas. Cell Tissue Res 197 (1979) 355-378
170. Robey E., Chang D., Itano A., Cado D., Alexander H., Lans D., et al. An activated form of Notch influences the choice between CD4 and CD8T cell lineages. Cell 87 (1996) 483-492
171. Roden A.C., Moser M.T., Tri S.D., Mercader M., Kuntz S.M., Dong H., et al. Augmentation of T cell levels and responses induced by androgen deprivation. J Immunol 173 (2004) 6098-6108
172. Rolleston H.D. The endocrine organs in health and disease (1936), Oxford University Press, London p. 439
173. Rosendahl A., Speletas M., Leandersson K., Ivars F., and Sideras P. Transforming growth factor-β- and activin-Smad signaling pathways are activated at distinct maturation stages of the thymopoeisis. Int Immunol 15 (2003) 1401-1414
174. Rossi S., Blazar B.R., Farrell C.L., Danilenko D.M., Lacey D.L., Weinberg K.I., et al. Keratinocyte growth factor preserves normal thymopoiesis and thymic microenvironment during experimental graft-versus-host disease. Blood 100 (2002) 682-691
175. - inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204 (2007) 1267-1272
176. Rowbotham N.J., Hager-Theodorides A.L., Furmanski A.L., and Crompton T. A novel role for Hedgehog in T-cell receptor signaling: implications for development and immunity. Cell Cycle 6 (2007) 2138-2142
177. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., and Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains. J Immunol 155 (1995) 1151-1164
178. Salomon B., Lenschow D.J., Rhee L., Ashourian N., Singh B., Sharpe A., et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12 (2000) 431-440
179. 1 in normal and pathological human thymuses. Eur J Immunol 14 (1984) 987-991
180. + cells, a discrete mouse thymic epithelial cell subset characterized by high molecular weight cytokeratin expression. Endocrinology 123 (1988) 2557-2564
181. Savino W., Villa-Verde D.M.S., and Lannes-Vieira J. Extracellular matrix proteins in intrathymic T cell migration and differentiation?. Immunol Today 14 (1993) 158-161
182. Savino W., Villa-Verde D.M., Alves L.A., and Dardenne M. Neuroendocrine control of the thymus. Ann N Y Acad Sci 840 (1998) 470-479
183. Savino W., Postel-Vinay M.C., Smaniotto S., and Dardenne M. The thymus gland: a target organ for growth hormone. Scand J Immunol 55 (2002) 442-452
184. Sempowski G.D., Hale L.P., Sundy J.S., Massey J.M., Koup R.A., Douek D.C., et al. Leukemia Inhibitory Factor, Oncostatin M, IL-6, and Stem Cell Factor mRNA expression in human thymus increases with age and is associated with thymic atrophy. J Immunol 164 (2000) 2180-2187
185. Serbedzija G.N., and McMahon A.P. Analysis of neural crest cell migration in Splotch mice using a neural crest-specific LacZ reporter. Dev Biol 185 (1997) 139-147
186. Shevach E.M. CD4+CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2 (2002) 389-400
187. Simon J. An essay on the physiology of the thymus gland (1845), Renshaw, London
188. Singer C.S. Galen on anatomical procedures (1956), Oxford University Press, London p. 250
189. Staal F.J., and Clevers H.C. Wnt signaling in the thymus. Curr Opin Immunol 15 (2003) 204-208
190. Su D.M., Navarre S., Oh W.J., Condie B.G., and Manley N.R. A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation. Nat Immunol 4 (2003) 1128-1135
191. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol 6 (2006) 127-135
192. Tanigaki K., Tsuji M., Yamamoto N., Han H., Tsukada J., Inoue H., et al. Regulation of αβ/γδT cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity 20 (2004) 611-622
193. Taub D.D., and Longo D.L. Insights into thymic aging and regeneration. Immunol Rev 205 (2005) 72-93
194. Taylor P.A., Friedman T.M., Korngold R., Noelle R.J., and Blazar B.R. Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40-CD40L costimulatory pathway results in the generation of a potent immune regulatory cell. Blood 99 (2002) 4601-4609
195. Timsit J., Savino W., Safieh B., Chanson P., Gagnerault M.C., Bach J.F., et al. effects of growth hormone and insulin-like growth factor 1 in thymic hormonal function in man. J Clin Endocrinol Metabol 75 (1992) 1251-1260
196. Toussaint-Demylle D., Scheiff J.M., and Haumont S. Thymic nurse cells: morphological study during their isolation from murine thymus. Cell Tissue Res 261 (1990) 115-123
197. Treiner E., Duban L., Bahram S., Radosavljevic M., Wanner V., Tilloy F., et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422 (2003) 164-169
198. Tsai P.T., Lee R.A., and Wu H. BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Blood 102 (2003) 3947-3953
199. Tseng Y.H., Kessler M.A., and Schuler L.A. Regulation of interleukin (IL)-1α, IL-1β and IL-6 expression by growth hormone and prolactin in bovine thymic stromal cells. Mol Cell Endocrinol 128 (1997) 117-127
200. Uehara S., Grinberg A., Farber J.M., and Love P.E. A role for CCR9 in T lymphocyte development and migration. J Immunol 168 (2002) 2811-2819
201. + thymocytes preferentially respond to CCL25. J Immunol 168 (2002) 134-142
202. Ueno T., Hara K., Willis M.S., Malin M.A., Höpken U.E., Gray D.H., et al. Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Immunity 16 (2002) 205:18
203. Ueno T., Saito F., Gray D.H., Kuse S., Hieshima K., Nakano H., et al. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. J Exp Med 200 (2004) 493-505
204. Urdahl K.B., Sun J.C., and Bevan M.J. Positive selection of MHC class Ib-restricted CD8+ T cells on hematopoietic cells. Nat Immunol 3 (2002) 772-779
205. Ushiki T. A scanning electron-microscopic study of the rat thymus with special reference to cell types and migration of lymphocytes into the general circulation. Cell Tissue Res 244 (1986) 285-298
206. van den Brink M.R., Alpdogan O., and Boyd R.L. Strategies to enhance T-cell reconstitution in immunocompromised patients. Nat Rev Immunol 4 (2004) 856-867
207. van Ewijk W. Cell surface topography of thymic microenvironments. Lab Invest 59 (1988) 579-590
208. Verrecchia F., and Mauviel A. Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol 118 (2002) 211-215
209. Vicente A., Varas A., Moreno J., Sacedón R., Jiménez E., and Zapata A.G. Ontogeny of rat thymic macrophages. Phenotypic characterization and possible relationships between different cell subsets. Immunology 85 (1995) 99-105
210. Vicente A., Varas A., Sacedón R., and Zapata A.G. Histogenesis of the epithelial component of rat thymus: an ultrastructural and immunohistological analysis. Anat Rec 244 (1996) 506-519
211. Villa-Verde D.M.S., Mello-Coelho V., Farias-de-Oliveira D.A., Dardenne M., and Savino W. Pleiotropic influence of triiodothyronine on thymus physiology. Endocrinology 133 (1993) 867-875
212. Viselli S.M., Stanziale S., Shults K., Kovacs W.J., and Olsen N.J. Castration alters peripheral immune function in normal male mice. Immunology 84 (1995) 337-342
213. von Boehmer H., Te H.S., and Kisielow P. The thymus selects the useful, neglects the useless and destroys the harmful. Immunol Today 10 (1989) 57-61
214. Wahl S.M., Hunt D.A., Wong H.L., Dougherty S., McCartney-Francis N., Wahl L.M., et al. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol 140 (1988) 3026-3032
215. Watanabe N., Hanabuchi S., Soumelis V., Yuan W., Ho S., de Waal Malefyt R., et al. Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4{thorn} T cell homeostatic expansion. Nat Immunol 5 (2004) 426-434
216. Watanabe N., Wang Y.H., Lee H.K., Ito T., Wang Y.H., Cao W., et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436 (2005) 1181-1185
217. Wekerle H., Ketelsen U.P., and Ernst M. Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization. J Exp Med 151 (1980) 925-944
218. Wendling O., Dennefeld C., Chambon P., and Mark M. Retinoid signaling is essential for patterning the endoderm of the third and fourth pharyngeal arches. Development 127 (2000) 1553-1562
219. Yoon S., Yoo H.J., Shim N.R., Baek S.Y., Kim B.S., Kim J.B., et al. Immunohistochemical characterization of macrophage and dendritic cell subpopulations of the spleen, thymus, tongue and heart in cyclophosphamide-induced immunosuppressed rat. Anat Histol Embryol 32 (2003) 80-88
220. Zaitseva M., Kawamura T., Loomis R., Goldstein H., Blauvelt A., and Golding H. Stromal-derived factor 1 expression in the human thymus. J Immunol 168 (2002) 2609-2617