The biology of recent thymic emigrants

Annual Review of Immunology

Volumn 31, Issue , 2013, Pages 31-50

  Fink, Pamela J ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Post thymic maturation; T cell development; T cell homeostasis

Indexed keywords

T LYMPHOCYTE RECEPTOR BETA CHAIN;

AGE; CELL HOMING; CELL MATURATION; CELLULAR DISTRIBUTION; HOMEOSTASIS; HUMAN; NATURAL KILLER CELL; NONHUMAN; PERSISTENT INFECTION; PHENOTYPE; POPULATION DYNAMICS; PRIORITY JOURNAL; RECENT THYMIC EMIGRANT; REVIEW; T LYMPHOCYTE; THYMECTOMY; THYMOCYTE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL AGING; CELL DIFFERENTIATION; CELL LINEAGE; CELL MOVEMENT; HUMANS; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; THYMUS GLAND;

EID: 84875489516     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-032712-100010     Document Type: Review

References (150)

1. Schwab SR, Cyster JG. 2007. Finding a way out: lymphocyte egress from lymphoid organs. Nat. Immunol. 8:1295-3011
2. Weinreich MA, Hogquist KA. 2008. Thymic emigration: when and how T cells leave home. J. Immunol. 181:2265-700
3. McCaughtry TM, Wilden MS, Hogquist KA. 2007. Thymic emigration revisited. J. Exp. Med. 204:2513-20
4. Carlson CM, Endrizzi BT, Wu J, Ding X, Weinreich MA, et al. 2006. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442:299-3022
5. Bai A, Hu H, Yeung M, Chen J. 2007. Kruppel-like factor 2 controls T cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription. J. Immunol. 178:7632-399
6. Zachariah MA, Cyster JG. 2010. Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction. Science 328:1129-355
7. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, et al. 2004. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355-60
8. Mou F, Praskova M, Xia F, van Buren D, Hock H, et al. 2012. The Mst1 and Mst2 kinases control activation of rho family GFPases and thymic egress of mature thymocytes. J. Exp. Med. 209:741-599
9. Scollay RG, Butcher EC, Weissman IL. 1980. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol. 10:210-188
10. Egerton M, Scollay R, Shortman K. 1990. Kinetics of mature T cell development in the thymus. Proc. Natl. Acad. Sci. USA 87:2579-822
11. Vrisekoop N, den Braber I, de Boer AB, Ruiter AF, Ackermans MT, et al. 2008. Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool. Proc. Natl. Acad. Sci. USA 105:6115-20
12. den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mogling R, et al. 2012. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36:288-977
13. Aspinall R, Andrew D. 2000. Thymic involution in aging. J. Clin. Immunol. 20:250-566
14. Zoller AL, Schnell FJ, Kersh GJ. 2007. Murine pregnancy leads to reduced proliferation of maternal thymocytes and decreased thymic emigration. Immunology 121:207-155
15. Berzins SP, Uldrich AP, Sutherland JS, Gill J, Miller JFAP, et al. 2002. Thymic regeneration: teaching an old immune system new tricks. Trends Mol. Med. 8:469-755
16. Chinn IK, Blackburn CC, Manley NR, Sempowski GD. 2012. Changes in primary lymphoid organs with aging. Semin. Immunol. 24(5):309-200
17. Berzins SP, Godfrey DI, Miller JFAP, Boyd RL. 1999. A central role for thymic emigrants in peripheral T cell homeostasis. Proc. Natl. Acad. Sci. USA 96:9787-911
18. Hale JS, Boursalian TE, Turk GL, Fink PJ. 2006. Thymic output in aged mice. Proc. Natl. Acad. Sci. USA 103:8447-522
19. Scollay R, Shortman K. 1984. Contribution of thymus lymphocytes to the peripheral lymphoid tissues and the effect of antigen on the rate of cell exit from the thymus. Am. J. Anat. 170:331-388
20. Kelly KA, Scollay R. 1991. The effect of peripheral immunization with Mls-1a on the emigration of antigen-specific cells from the thymus. Eur. J. Immunol. 21:43-477
21. Uldrich AP, Berzins SP, Malin MA, Bouillet P, Strasser A, et al. 2006. Antigen challenge inhibits thymic emigration. J. Immunol. 176:4553-611
22. Gabor MJ, Godfrey DI, Scollay R. 1997. Recent thymic emigrants are distinct from most medullary thymocytes. Eur. J. Immunol. 27:2010-155
23. Berzins SP, Boyd RL, Miller JFAP. 1998. The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. J. Exp. Med. 187:1839-488
24. Fink PJ, Hendricks DW. 2011. Post-thymic maturation: young T cells assert their individuality. Nat. Rev. Immunol. 11:544-488
25. Butcher EC, Scollay RG, Weissman IL. 1980. Direct fluorescent labeling of cells with fluorescein or rhodamine isothiocyanate. II. Potential application to studies of lymphocyte migration and maturation. J. Immunol. Methods 37:109-211
26. Hale JS, Fink PJ. 2009. Back to the thymus: peripheral T cells come home. Immunol. Cell Biol. 87:58-644
27. Tough DF, Sprent J. 1994. Turnover of naive-andmemory-phenotypeTcells. J. Exp.Med. 179:1127-355
28. Lee CK, Kim K, Welniak LA, Murphy WJ, Muegge K, Durum SK. 2001. Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. Blood 97:1360-699
29. Kuwata N, Igarashi H, Ohmura T, Aizawa S, Sakaguchi N. 1999. Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J. Immunol. 163:6355-599
30. Yu W, Nagaoka H, Jankovic M, Misulovin Z, Suh H, et al. 1999. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization. Nature 400:682-877
31. Hassan J, Reen DJ. 2001. Human recent thymic emigrants -identification, expansion, and survival characteristics. J. Immunol. 167:1970-766
32. Cooper CJ, OrrMT, McMahan CJ, Fink PJ. 2003. T cell receptor revision does not solely target recent thymic emigrants. J. Immunol. 171:226-333
33. Boursalian TE, Golub J, Soper DM, Cooper CJ, Fink PJ. 2004. Continued maturation of thymic emigrants in the periphery. Nat. Immunol. 5:418-25
34. Makaroff LE, Hendricks DW, Niec RE, Fink PJ. 2009. Postthymic maturation influences the CD8 T cell response to antigen. Proc. Natl. Acad. Sci. USA 106:4799-8044
35. Houston EG Jr, Higdon LE, Fink PJ. 2011. Recent thymic emigrants are preferentially incorporated only into the depleted T-cell pool. Proc. Natl. Acad. Sci. USA 108:5366-711
36. Kelly KA, Scollay R. 1990. Analysis of recent thymic emigrants with subset-and maturity-related markers. Int. Immunol. 2:419-255
37. Kong FK, Chen CL, Cooper MD. 1998. Thymic function can be accurately monitored by the level of recent T cell emigrants in the circulation. Immunity 8:97-1044
38. Katevuo K, Vainio O. 1996. Thymocyte emigration in the chicken: an over-representation of CD4+ cells over CD8-in the periphery. Immunology 89:419-233
39. Miyaska M, Pabst R, Dudler L, Cooper M, Yamaguchi K. 1990. Characterization of lymphatic and venous emigrants from the thymus. Thymus 16:29-433
40. Binns RM, Pabst R, Licence ST. 1988. Subpopulations of T lymphocytes emigrating in venous blood draining pig thymus labelled in vivo with fluorochrome. Immunology 63:261-677
41. Hosseinzadeh H, Goldschneider I. 1993. Recent thymic emigrants in the rat express a unique antigenic phenotype and undergo post-thymic maturation in peripheral lymphoid tissues. J. Immunol. 150:1670-799
42. Yang C, Bell EB. 1992. Functional maturation of recent thymic emigrants in the periphery: development of alloreactivity correlates with the cyclic expression of CD45RC isoforms. Eur. J. Immunol. 22:2261-699
43. Kampinga J, Groen H, Klatter FA, Pater JM, van Petersen AS, et al. 1997. Post-thymic T-cell development in the rat. Thymus 24:173-2000
44. Thiele HG, Haag F. 2001. The RT6 system of the rat: developmental, molecular and functional aspects. Immunol. Rev. 184:96-1088
45. Livak F, Schatz DG. 1996. T-cell receptor α locus V(D)J recombination by-products are abundant in thymocytes and mature T cells. Mol. Cell. Biol. 16:609-188
46. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, et al. 1998. Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690-95
47. Kong FK, Chen CL, Six A, Hockett RD, Cooper CJ. 1999. T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool. Proc. Natl. Acad. Sci. USA 96:1536-400
48. Zhang L, Lewin SR, Markowits M, Lin HH, Skulsky E, et al. 1999. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J. Exp. Med. 190:725-322
49. Hazenberg MD, Otto SA, Cohen Stuart JWT, Verschuren JMA, Borleffs JCC, et al. 2000. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat. Med. 6:1036-422
50. Hazenberg MD, Verschuren MCM, Hamann D, Miedema F, van Dongen JJ. 2001. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J. Mol. Med. 79:631-400
51. Kimmig S, Przybylski CA, Schmidt CA, Laurisch K, Mowes B, et al. 2002. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195:789-944
52. Hazenberg MD, Borghans JAM, de Boer RJ, Miedema F. 2003. Thymic output: a bad TREC record. Nat. Immunol. 4:97-999
53. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, et al. 2004. HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 21:757-688
54. Ribeiro RM, Perelson AS. 2007. Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) data. Immunol. Rev. 216:21-344
55. Lorenzi AR, Patterson AM, Pratt A, Jefferson M, Chapman CE, et al. 2008. Determination of thymic function directly from peripheral blood: a validated modification to an established method. J. Immunol. Methods 339:185-944
56. Bains I, Thiebaut R, Yates AJ, Callard R. 2009. Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output. J. Immunol. 183:4329-366
57. Ferrando-Martinez S, Franco JM, Ruiz-Mateos E, Hernandez A, Ordonez A, et al. 2010. A reliable and simplified sj/β-TREC ratio quantification method for human thymic output measurement. J. Immunol. Methods 352:111-177
58. Junge S, Kloechener-Gruissem B, Zufferey R, Keisker A, Salgo B, et al. 2007. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur. J. Immunol. 37:3270-800
59. Kohler S, Thiel A. 2009. Life after the thymus: CD31+ and CD31 human naive CD4+ T-cell subsets. Blood 113:769-744
60. Tanaskovic S, Fernandez S, Price P, Lee S, French MA. 2010. CD31 (PECAM-1) is a marker of recent thymic emigrants amongCD4+ T-cells, but notCD8-T-cells or γδT-cells, inHIV patients responding to ART. Immunol. Cell Biol. 88:321-277
61. Haines CJ, Giffon TD, Lu LS, Lu X, Lavigne-Tessier M, et al. 2009. Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function. J. Exp. Med. 206:275-85
62. Lewis DB, Haines C, Ross D. 2011. Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility. J. Perinatol. 31(Suppl. 1):S72-811
63. McFarlandRD, DouekDC, Koup RA, Picker LJ. 2000. Identification of a human recent thymic emigrant phenotype. Proc. Natl. Acad. Sci. USA 97:4215-200
64. Mackall CL, Hakim FT, Gress RE. 1997. Restoration of T-cell homeostasis after T-cell depletion. Semin. Immunol. 9:339-466
65. Di Rosa F, Ramaswamy S, Ridge JP, Matzinger P. 1999. On the lifespan of virgin T lymphocytes. J. Immunol. 163:1253-577
66. YagerEJ, AhmedM, LanzerK, Randall TD, WoodlandDL, BlackmanMA. 2008. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J. Exp. Med. 205:711-233
67. BlackmanMA, WoodlandDL. 2011. The narrowing of the CD8 T cell repertoire in old age. Curr. Opin. Immunol. 23:537-422
68. JenkinsMK, Chu HH, McLachlan JB, Moon JJ. 2010. On the composition of the preimmune repertoire of T cells specific for peptide-major histocompatibility complex ligands. Annu. Rev. Immunol. 28:275-944
69. Lynch HE, Goldberg GL, Chidgey A, van den Brink MRM, Boyd RL, Sempowski GD. 2009. Thymic involution and immune reconstitution. Trends Immunol. 30:366-733
70. Gurkan S, Luan Y, Dhillon N, Allam SR, Montague T, et al. 2010. Immune reconstitution following rabbit antithymocyte globulin. Am. J. Transplant. 10:2132-411
71. Bloemers BLP, Bont L, de Weger RA, Otto SA, Borghans JA, Tesselaar K. 2011. Decreased thymic output accounts for decreased naive T cell numbers in children with Down Syndrome. J. Immunol. 186:4500-77
72. Heitger A, Greinix H, Mannhalter C, Mayerl D, Kern H, et al. 2000. Requirement of residual thymus to restore normal T cell subsets after human allogeneic bone marrow transplantation. Transplantation 69:2366-733
73. Roux E, Dumont-Girard F, Starobinski M, Siegrist CA, Helg C, et al. 2000. Recovery of immune reactivity after T cell-depleted bone marrow transplantation depends on thymic activity. Blood 96:2299-3033
74. Talvensaari K, Clave E, Douay C, Rabian C, Garderet L, et al. 2002. A broad T cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation. Blood 99:1458-644
75. Toubert A, Glauzy S, Douay C, Clave E. 2012. Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again. Tissue Antigens 79:83-899
76. Murano PA, Douek DC, Packer A, Chung K, Guenaga FJ, et al. 2005. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J. Exp. Med. 201:805-166
77. Sauce D, Larsen M, Fastenackels S, Duperrier A, Keller M, et al. 2009. Evidence of premature immune aging in patients thymectomized during early childhood. J. Clin. Investig. 119:3070-788
78. Appay V, Sauce D, Prelog M. 2010. The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. Aging 2:78-811
79. Goronzy J, Weyand CM. 2001. Thymic function and peripheral T cell homeostasis in rheumatoid arthritis. Trends Immunol. 22:251-555
80. Vezys V, Masopust D, Kemball CC, Barber DL, O'Mara LA, et al. 2006. Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J. Exp. Med. 203:2263-699
81. Miller NE, Bonczyk JR, Nakayama Y, Suresh M. 2005. Role of thymic output in regulating CD8 T-cell homeostasis during acute and chronic viral infection. J. Virol. 79:9419-299
82. Jelley-Gibbs DM, Brown DM, Dibble J, Haynes L, Eaton SM, Swain SL. 2005. Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med. 202:697-7066
83. Douek DC. 2003. Disrupting T cell homeostasis: howHIV-1 infection causes disease. AIDS Rev. 5:172-777
84. Williams KM, Hakim FT, Gress RE. 2007. T cell immune reconstitution following lymphodepletion. Semin. Immunol. 19:318-300
85. Hatzakis A, Touloumi G, Karanicolas R, Karafoulidou A, Mandalaki T, et al. 2000. Effect of recent thymic emigrants on progression of HIV-1 disease. Lancet 355:599-6044
86. Yang Y, Al-Mozaini M, Buzon MJ, Beamon J, Gerrando M, et al. 2012. CD4 T cell regeneration in HIV-1 elite controllers. AIDS 26:701-66
87. Steffens CM, Smith KY, Landay A, Shott S, Truckenbrod A, et al. 2001. T cell receptor excision circle (TREC) content following maximum HIV suppression is equivalent in HIV-infected and HIVuninfected individuals. AIDS 15:1757-644
88. Teixeira L, Valdez H, McCune JM, Koup RA, Badley AD, et al. 2001. Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS 15:1749-566
89. Douek DC, Betts MR, Hill BJ, Little SJ, Lempicki R, et al. 2001. Evidence for increased T cell turnover and decreased thymic output in HIV infection. J. Immunol. 167:6663-688
90. Fabre-Mersseman V, Dutrieux J, Louise A, Rozlan S, Lamine A, et al. 2011. CD4+ recent thymic emigrants are infected by HIV in vivo, implication for pathogenesis. AIDS 25:1153-622
91. Hogquist KA, Weinreich MA, Jameson SC. 2008. T-cell migration: Kruppled T cells move again. Immunol. Cell Biol. 86:297-988
92. Scollay R. 1982. Thymus cell migration: cells migrating from thymus to peripheral lymphoid organs have a "mature" phenotype. J. Immunol. 128:1566-700
93. Staton TL, Habtezion A, Winslow MM, Sato T, Love PE, Butcher EC. 2006. CD8-recent thymic emigrants home to and efficiently repopulate the small intestine epithelium. Nat. Immunol. 7:482-888
94. Holder JE, Kimpton WG, Washington EA, Cahill RNP. 1999. L-selectin expression on thymic emigrants defines two distinct tissue-migration pathways. Immunology 98:422-266
95. Flo J, Massouh E. 1997. Age-related changes of naive and memory CD4 rat lymphocyte subsets in mucosal and systemic lymphoid organs. Dev. Comp. Immunol. 21:443-533
96. Iwakoshi NN, Goldschneider I, Tausche F, Modres JP, Rossini AA, Greiner DL. 1998. High frequency of apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats. J. Immunol. 160:5838-500
97. Luettig B, Sponholz A, Heerwagen C, Bode U, Westermann J. 2001. Recent thymic emigrants (CD4+) continuously migrate through lymphoid organs: within the tissue they alter surface molecule expression. Scand. J. Immunol. 53:563-711
98. Jimenez E, Sacedon R, Vicente A, Hernandez-Lopez C, Zapata AG, Varas A. 2002. Rat peripheral CD4+CD8-T lymphocytes are partially immunocompetent thymus-derived cells that undergo postthymic maturation to become functionally mature CD4+ T lymphocytes. J. Immunol. 168:5005-133
99. Staton TL, Johnston B, Butcher EC, Campbell DJ. 2004. Murine CD8-recent thymic emigrants are αE integrin-positive and CC chemokine ligand 25 responsive. J. Immunol. 172:7282-888
100. SchonMP, Arya A, Murphy EA, Adams CM, Strauch UG, et al. 1999. Mucosal T lymphocyte numbers are selectively reduced in integrin αE (CD103)-deficient mice. J. Immunol. 162:6641-499
101. Wurbel MA, Malissen M, Guy-Grand D, Meffre E, Nussenzweig MC. 2001. Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T-and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes. Blood 98:2626-322
102. Bourgeois C, Hao Z, Rajewsky K, Potocnik AJ, Stockinger B. 2008. Ablation of thymic export causes accelerated decay of naive CD4 T cells in the periphery because of activation by environmental antigen. Proc. Natl. Acad. Sci. USA 105:8691-966
103. Elgbratt K, Kurlberg G, Hahn-Zohric M, Hornquist EH. 2010. Rapid migration of thymic emigrants to the colonic mucosa in ulcerative colitis patients. Clin. Exp. Immunol. 162:325-366
104. Schnell FJ, Kersh GJ. 2005. Control of recent thymic emigrant survival by positive selection signals and early growth response gene 1. J. Immunol. 175:2270-777
105. Li O, Zheng P, Liu Y. 2004. CD24 expression on T cells is required for optimal T cell proliferation in lymphopenic host. J. Exp. Med. 200:1083-899
106. Thomas-Vaslin V, Altes HK, de Boer RJ, Klatzmann D. 2008. Comprehensive assessment and mathematical modeling of T cell population dynamics and homeostasis. J. Immunol. 180:2240-500
107. McHeyzer-Williams LJ, McHeyzer-Williams MG. 2004. Developmentally distinct Th cells control plasma cell production in vivo. Immunity 20:231-422
108. Thangavelu G, Parkman JC, Ewen CL, Uwiera RR, Baldwin TA, Anderson CC. 2011. Programmed death-1 is required for systemic self-tolerance in newly generated T cells during the establishment of immune homeostasis. J. Autoimmun. 36:301-122
109. Hassan J, Reen DJ. 2002. IL-7 and homeostasis of recent thymic emigrants. Trends Immunol. 23:126-277
110. Swainson L, Kinet S, Mongellaz C, Sourisseau M, Henriques T, Taylor N. 2007. IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway. Blood 109:1034-422
111. Opiela SJ, Koru-Sengul T, Adkins B. 2009. Murine neonatal recent thymic emigrants (RTE) are phenotypically and functionally distinct from adult RTE. Blood 113:5635-43
112. Scollay R, Chen WF, Shortman K. 1984. The functional capabilities of cells leaving the thymus. J. Immunol. 132:25-300
113. Ramsdell F, Jenkins MK, Dinh Q, Fowlkes BJ. 1991. The majority of CD4+CD8 thymocytes are functionally immature. J. Immunol. 147:1779-855
114. Piguet PF, Irle C, Kollatte E, Vassalli P. 1981. Post-thymicTlymphocyte maturation during ontogenesis. J. Exp. Med. 154:581-933
115. Priyadharshini B, Welsh RM, Greiner DL, Gerstein RM, Brehm MA. 2010. Maturation-dependent licensing of naive T cells for rapid TNF production. PLoS ONE 5:e150388
116. Joshi NS, Kaech SM. 2008. Effector CD8 T cell development: a balancing act between memory cell potential and terminal differentiation. J. Immunol. 180:1309-155
117. Chang JF, Thomas CA 3rd, Kung JT. 1991. Induction of high level IL-2 production in CD4+8 T helper lymphocytes requires post-thymic development. J. Immunol. 147:851-599
118. Bendelac A, Matzinger P, Seder RA, Paul WE, Schwartz RH. 1992. Activation events during thymic selection. J. Immunol. 175:731-422
119. Imanishi K, Seo K, Kato H, Miyoshi-Akiyama T, Zhang RH, et al. 1998. Post-thymic maturation of migrating human thymic single-positive T cells: thymic CD1a CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord bloodCD4+ Tcells. J. Immunol. 160:112-199
120. Hendricks DW, Fink PJ. 2011. Recent thymic emigrants are biased against the T-helper type 1 and toward the T-helper type 2 effector lineage. Blood 117:1239-49
121. Rose S, Lichtenheld M, Foote MR, Adkins B. 2007. Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. J. Immunol. 178:2667-788
122. Godfrey DI, Stankovic S, Baxter AG. 2010. Raising the NKT family. Nat. Immunol. 11:197-2066
123. Milpied P, Massot B, Renand A, Diem S, Herbelin A, et al. 2011. IL-17-producing invariantNKTcells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression. Blood 118:2993-30022
124. Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. 1992. CD28-mediated signalling costimulates murine T cells and prevents induction of anergy of T-cell clones. Nature 356:607-99
125. Wells AD. 2009. New insights into the molecular basis of T cell anergy: anergy factors, avoidance sensors, and epigenetic imprinting. J. Immunol. 182:7331-411
126. Zhu J, PaulWE. 2008. CD4 T cells: fates, functions, and faults. Blood 112:1557-699
127. Houston EG Jr, Nechanitzky R, Fink PJ. 2008. Cutting edge: contact with secondary lymphoid organs drives postthymic T cell maturation. J. Immunol. 181:5213-17
128. Barbee SD, Alberola-Ila J. 2005. Phosphatidylinositol 3-kinase regulates thymic exit. J. Immunol. 174:1230-388
129. Schacker TW, Brenchley JM, Beilman GJ, Reilly C, Pambuccian SE, et al. 2006. Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection. Clin. Vaccine Immunol. 13:556-600
130. Houston EG Jr, Fink PJ. 2009. MHC drives TCR repertoire shaping, but not maturation, in recent thymic emigrants. J. Immunol. 183:7244-499
131. Surh CD, Sprent J. 2008. Homeostasis of naive and memory T cells. Immunity 29:848-622
132. Takada K, Jameson SC. 2009. Naive T cell homeostasis: from awareness of space to a sense of place. Nat. Rev. Immunol. 9:823-322
133. FryTJ, Mackall CL. 2005. Themany faces of IL-7: from lymphopoiesis to peripheralTcellmaintenance. J. Immunol. 174:6571-766
134. Link A, Vogt TK, Favre S, BritschgiMR, Acha-Orbea H, et al. 2007. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 8:1255-655
135. Houston EGJ, Boursalian TE, Fink PJ. 2012. Homeostatic signals do not drive post-thymic T cell maturation. Cell. Immunol. 274:39-455
136. Pajerowski AG, Nguyen C, Aghajanian H, Shapiro MJ, Shapiro VS. 2009. NKAP is a transcriptional repressor of notch signaling and is required for T cell development. Immunity 30:696-7077
137. Hsu FC, Pajerowski AG, Nelson-Holte M, Sundsbak R, Shapiro VS. 2011. NKAP is required for T cell maturation and acquisition of functional competency. J. Exp. Med. 208:1291-304
138. Liu G, Yang K, Burns S, Shrestha S, Chi H. 2010. The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nat. Immunol. 11:1047-566
139. Thomson AG, Turnquist HR, Raimondi G. 2009. Immunoregulatory functions of mTOR inhibition. Nat. Rev. Immunol. 9:324-377
140. Alferink J, Tafuri A, Vestweber D, Hallmann R, Hammerling GJ, Arnold B. 1998. Control of neonatal tolerance to tissue antigens by peripheral T cell trafficking. Science 282:1338-411
141. Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, et al. 2008. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 321:843-477
142. Lukacs-Kornek V, Turley SJ. 2011. Self-antigen presentation by dendritic cells and lymphoid stroma and its implications for autoimmunity. Curr. Opin. Immunol. 23:138-455
143. Macian F, Garcia-Cozar F, Im SH, Horton HF, Byrne MC, Rao A. 2002. Transcriptional mechanisms underlying lymphocyte tolerance. Cell 109:719-311
144. Alter SE, Song HK, Fathman CG. 1993. Evidence that clonal anergy is induced in thymic migrant cells after anti-CD4-mediated transplantation tolerance. Transplantation 56:633-388
145. Armengol MP, Sabater L, FernandezM, RuizM, AlonsoN, et al. 2008. Influx of recent thymic emigrants into autoimmune thyroid disease glands in humans. Clin. Exp. Immunol. 153:338-500
146. Allison JP, HavranWL. 1991. The immunobiology of T cells with invariant γδantigen receptors. Annu. Rev. Immunol. 9:679-7055
147. Linton PJ, Dorshkind K. 2004. Age-related changes in lymphocyte development and function. Nat. Immunol. 5:133-399
148. Nikolich-Zugich J. 2005. T cell aging: naive but not young. J. Exp. Med. 201:837-400
149. Clise-Dwyer K, Huston GE, Buck AL, Duso DK, Swain SL. 2007. Environmental and intrinsic factors lead to antigen unresponsiveness in CD4+ recent thymic emigrants from aged mice. J. Immunol. 178:1321-31
150. Aw D, Silva AB, Palmer DB. 2009. Is thymocyte development functional in the aged? Aging 1:146-533