Regulatory T-cell development in the human thymus

Frontiers in Immunology

Volumn 6, Issue JUL, 2015, Pages

  Caramalho, Íris ^a   Nunes Cabaço, Helena ^a   Foxall, Russell B ^a   Sousa, Ana E ^a  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

FOXP3; Human thymic defects; Human thymus; Primary immunodeficiency; Regulatory T cell development; Regulatory T cells

Indexed keywords

CYTOKINE; INDUCIBLE T CELL COSTIMULATOR; TRANSCRIPTION FACTOR FOXP3;

AUTOIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL LINEAGE; CELL MATURATION; DENDRITIC CELL; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; MAJOR HISTOCOMPATIBILITY COMPLEX; PHENOTYPE; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SHORT SURVEY; SIGNAL TRANSDUCTION; THYMOCYTE; THYMUS;

EID: 84938506526     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00395     Document Type: Short Survey

References (70)

1. Sakaguchi S, Miyara M, Constantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol (2010) 10:490-500. doi:10.1038/nri2785
2. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet (2001) 27:20-1. doi:10.1038/83713
3. Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet (2001) 27:18-20. doi:10.1038/83707
4. Seidel MG, Fritsch G, Lion T, Jurgens B, Heitger A, Bacchetta R, et al. Selective engraftment of donor CD4+25high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation. Blood (2009) 113:5689-91. doi:10.1182/blood-2009-02-206359
5. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T Cells: mechanisms of differentiation and function. Annu Rev Immunol (2012) 30:531-64. doi:10.1146/annurev.immunol.25.022106.141623
6. Hsieh CS, Lee HM, Lio CW. Selection of regulatory T cells in the thymus. Nat Rev Immunol (2012) 12:157-67. doi:10.1038/nri3155
7. Legrand N, Weijer K, Spits H. Experimental models to study development and function of the human immune system in vivo. J Immunol (2006) 176:2053-8. doi:10.4049/jimmunol.176.4.2053
8. Notarangelo LD. Combined immunodeficiencies with nonfunctional T lymphocytes. Adv Immunol (2014) 121:121-90. doi:10.1016/B978-0-12-800100-4. 00004-0
9. Pignata C, D'Assante R, Sousa AE. Thymic stromal alterations and genetic disorders of immune system. Front Immunol (2015) 6:81. doi:10.3389/fimmu.2015.00081
10. Davies EG. Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol (2013) 4:322. doi:10.3389/fimmu.2013.00322
11. Sullivan KE, McDonald-McGinn D, Zackai EH. CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia. Clin Diagn Lab Immunol (2002) 9:1129-31. doi:10.1128/CDLI.9.5.1129-1131.2002
12. McLean-Tooke A, Barge D, Spickett GP, Gennery AR. Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol (2008) 122:e-7. doi:10.1016/j.jaci.2008.03.033
13. Klocperk A, Grecová J, Šišmová K, Kayserová J, Fronková E, Šedivá A. Helios expression in T-regulatory cells in patients with Di George syndrome. J Clin Immunol (2014) 34:864-70. doi:10.1007/s10875-014-0071-y
14. Poliani PL, Facchetti F, Ravanini M, Gennery AR, Villa A, Roifman CM, et al. Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. Blood (2009) 114:105-8. doi:10.1182/blood-2009-03-211029
15. Kekalainen E, Tuovinen H, Joensuu J, Gylling M, Franssila R, Pontynen N, et al. A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Immunol (2007) 178:1208-15. doi:10.4049/jimmunol.178.2.1208
16. Laakso SM, Laurinolli TT, Rossi LH, Lehtoviita A, Sairanen H, Perheentupa J, et al. Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population. J Autoimmun (2010) 35:351-7. doi:10.1016/j.jaut.2010.07.008
17. Arstila TP, Jarva H. Human APECED; a sick thymus syndrome? Front Immunol (2013) 4:313. doi:10.3389/fimmu.2013.00313
18. Machnes-Maayan D, Lev A, Katz U, Mishali D, Vardi A, Simon AJ, et al. Insight into normal thymic activity by assessment of peripheral blood samples. Immunol Res (2015) 61:198-205. doi:10.1007/s12026-014-8558-4
19. Paiva RS, Lino AC, Bergman ML, Caramalho I, Sousa AE, Zelenay S, et al. Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery. Proc Natl Acad Sci U S A (2013) 110:6494-9. doi:10.1073/pnas.1221955110
20. Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, et al. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood (2011) 117:688-96. doi:10.1182/blood-2010-06-292490
21. Albuquerque AS, Marques JG, Silva SL, Ligeiro D, Devlin BH, Dutrieux J, et al. Human FOXN1-deficiency is associated with aß double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation. PLoS One (2012) 7:e37042. doi:10.1371/journal.pone.0037042.g005
22. Chinn IK, Milner JD, Scheinberg P, Douek DC, Markert ML. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3-T cells in complete DiGeorge anomaly. Clin Exp Immunol (2013) 173:140-9. doi:10.1111/cei.12088
23. Nunes-Cabaço H, Sousa AE. Repairing thymic function. Curr Opin Organ Transplant (2013) 18:363-8. doi:10.1097/MOT.0b013e3283615df9
24. Haynes BF, Heinly CS. Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment. J Exp Med (1995) 181:1445-58. doi:10.1084/jem.181.4.1445
25. Farley AM, Morris LX, Vroegindeweij E, Depreter MLG, Vaidya H, Stenhouse FH, et al. Dynamics of thymus organogenesis and colonization in early human development. Development (2013) 140:2015-26. doi:10.1242/dev.087320
26. Haddad R, Guimiot F, Six E, Jourquin F, Setterblad N, Kahn E, et al. Dynamics of thymus-colonizing cells during human development. Immunity (2006) 24:217-30. doi:10.1016/j.immuni.2006.01.008
27. Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H. Development and activation of regulatory T cells in the human fetus. Eur J Immunol (2005) 35:383-90. doi:10.1002/eji.200425763
28. Darrasse-Jèze G, Marodon G, Salomon BL, Catala M, Klatzmann D. Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses. Blood (2005) 105:4715-21. doi:10.1182/blood-2004-10-4051
29. Michaelsson J, Mold JE, McCune JM, Nixon DF. Regulation of T cell responses in the developing human fetus. J Immunol (2006) 176:5741-8. doi:10.4049/jimmunol.176.10.5741
30. Annunziato F, Cosmi L, Liotta F, Lazzeri E, Manetti R, Vanini V, et al. Phenotype, localization, and mechanism of suppression of CD4+CD25+ human thymocytes. J Exp Med (2002) 196:379-87. doi:10.1084/jem.20020110
31. Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, et al. Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood (2003) 102:4107-14. doi:10.1182/blood-2003-04-1320
32. Liotta F, Cosmi L, Romagnani P, Maggi E, Romagnani S, Annunziato F. Functional features of human CD25+ regulatory thymocytes. Microbes Infect (2005) 7:1017-22. doi:10.1016/j.micinf.2005.03.024
33. Tuovinen H, Kekäläinen E, Rossi LH, Puntila J, Arstila TP. Cutting edge: human CD4-CD8-thymocytes express FOXP3 in the absence of a TCR. J Immunol (2008) 180:3651-4. doi:10.4049/jimmunol.180.6.3651
34. Tuovinen H, Pekkarinen PT, Rossi LH, Mattila I, Arstila TP. The FOXP3+ subset of human CD4+CD8+ thymocytes is immature and subject to intrathymic selection. Immunol Cell Biol (2008) 86:523-9. doi:10.1038/icb.2008.36
35. Nunes-Cabaço H, Ribot JC, Caramalho Í, Serra-Caetano A, Silva-Santos B, Sousa AE. Foxp3 induction in human and murine thymus precedes the CD4+ CD8+ stage but requires early T-cell receptor expression. Immunol Cell Biol (2010) 88:523-8. doi:10.1038/icb.2010.4
36. Nunes-Cabaço H, Caramalho Í, Sepúlveda N, Sousa AE. Differentiation of human thymic regulatory T cells at the double positive stage. Eur J Immunol (2011) 41:3604-14. doi:10.1002/eji.201141614
37. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature (2005) 436:1181-5. doi:10.1038/nature03886
38. Martin-Gayo E, Sierra-Filardi E, Corbi AL, Toribio ML. Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development. Blood (2010) 115:5366-75. doi:10.1182/blood-2009-10-248260
39. Caramalho Í, Nunes-Silva V, Pires AR, Mota C, Pinto AI, Nunes-Cabaço H, et al. Human regulatory T-cell development is dictated by interleukin-2 and-15 expressed in a non-overlapping pattern in the thymus. J Autoimmun (2015) 56:98-110. doi:10.1016/j.jaut.2014.11.002
40. Tuovinen H, Salminen JT, Arstila TP. Most human thymic and peripheral-blood CD4+CD25+ regulatory T cells express 2 T-cell receptors. Blood (2006) 108:4063-70. doi:10.1182/blood-2006-04-016105
41. Stephens LA, Mottet C, Mason D, Powrie F. Human CD4+ CD25+ thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur J Immunol (2001) 31:1247-54. doi:10.1002/1521-4141(200104)31:4<1247:: AID-IMMU1247>3.0.CO;2-M
42. Wing K, Ekmark A, Karlsson H, Rudin A, Suri-Payer E. Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood. Immunology (2002) 106:190-9. doi:10.1046/j.1365-2567.2002.01412.x
43. Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, Bover L, et al. Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity (2008) 28:870-80. doi:10.1016/j.immuni.2008.03.018
44. Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, et al. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol (2015) 16:628-34. doi:10.1038/ni.3150
45. 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 develop at the double-positive thymic stage. Proc Natl Acad Sci U S A (2006) 103:8453-8. doi:10.1073/pnas.0603086103
46. Ribot J, Enault G, Pilipenko S, Huchenq A, Calise M, Hudrisier D, et al. Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection. J Immunol (2007) 179:6741-8. doi:10.4049/jimmunol.179.10.6741
47. Liston A, Nutsch KM, Farr AG, Lund JM, Rasmussen JP, Koni PA, et al. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc Natl Acad Sci U S A (2008) 105:11903-8. doi:10.1073/pnas.0801506105
48. Lee HM, Hsieh CS. Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset. J Immunol (2009) 183:2261-6. doi:10.4049/jimmunol.0901304
49. Hanabuchi S, Ito T, Park WR, Watanabe N, Shaw JL, Roman E, et al. Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol (2010) 184:2999-3007. doi:10.4049/jimmunol.0804106
50. Michie SA, Rouse RV. Traffic of mature lymphocytes into the mouse thymus. Thymus (1989) 13:141-8.
51. Kirberg J, Bosco N, Deloulme JC, Ceredig R, Agenès F. Peripheral T lymphocytes recirculating back into the thymus can mediate thymocyte positive selection. J Immunol (2008) 181:1207-14. doi:10.4049/jimmunol.181.2.1207
52. Nazzal D, Gradolatto A, Truffault F, Bismuth J, Berrih-Aknin S. Human thymus medullary epithelial cells promote regulatory T-cell generation by stimulating interleukin-2 production via ICOS ligand. Cell Death Dis (2014) 5:e1420. doi:10.1038/cddis.2014.377
53. Kasow KA, Chen XH, Knowles J, Wichlan D, Handgretinger R, Riberdy JM. Human CD4+CD25+ regulatory T cells share equally complex and comparable repertoires with CD4+CD25-counterparts. J Immunol (2004) 172:6123-8. doi:10.4049/jimmunol.172.10.6123
54. Fazilleau N, Bachelez H, Gougeon ML, Viguier M. Cutting edge: size and diversity of CD4+CD25high Foxp3+ regulatory T cell repertoire in humans: evidence for similarities and partial overlapping with CD4+CD25-T Cells. J Immunol (2007) 179:3412-6. doi:10.4049/jimmunol.179.6.3412
55. Mantel PY, Ouaked N, Ruckert B, Karagiannidis C, Welz R, Blaser K, et al. Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol (2006) 176:3593-602. doi:10.4049/jimmunol.176.6.3593
56. Rajpal A, Cho YA, Yelent B, Koza-Taylor PH, Li D, Chen E, et al. Transcriptional activation of known and novel apoptotic pathways by Nur orphan steroid receptor. EMBO J (2003) 22:6526-36. doi:10.1093/emboj/cdg620
57. Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, et al. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2-/-gammac-/-mice. Blood (2006) 108:238-45. doi:10.1182/blood-2006-01-0190
58. Poliani PL, Fontana E, Roifman CM, Notarangelo LD. ζ Chain-associated protein of 70 kDa (ZAP70) deficiency in human subjects is associated with abnormalities of thymic stromal cells: implications for T-cell tolerance. J Allergy Clin Immunol (2013) 131:e-600. doi:10.1016/j.jaci.2012.11.002
59. Hutton JF, Gargett T, Sadlon TJ, Bresatz S, Brown CY, Zola H, et al. Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells. J Leukoc Biol (2008) 85:445-51. doi:10.1189/jlb.1008620
60. Walters SN, Webster KE, Daley S, Grey ST. A role for intrathymic B cells in the generation of natural regulatory T cells. J Immunol (2014) 193:170-6. doi:10.4049/jimmunol.1302519
61. Lu FT, Yang W, Wang YH, Ma HD, Tang W, Yang JB, et al. Thymic B cells promote thymus-derived regulatory T cell development and proliferation. J Autoimmun (2015) 61:62-72. doi:10.1016/j.jaut.2015.05.008
62. Jebbawi F, Fayyad-Kazan H, Merimi M, Lewalle P, Verougstraete JC, Leo O, et al. A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes. J Transl Med (2014) 12:218. doi:10.1186/s12967-014-0218-x
63. Allakhverdi Z, Fitzpatrick D, Boisvert A, Baba N, Bouguermouh S, Sarfati M, et al. Expression of CD103 identifies human regulatory T-cell subsets. J Allergy Clin Immunol (2006) 118:1342-9. doi:10.1016/j.jaci.2006.07.034
64. Kutlesa S, Wessels JT, Speiser A, Steiert I, Müller CA, Klein G. E-cadherinmediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation. J Cell Sci (2002) 115:4505-15. doi:10.1242/jcs.00142
65. Tang XL, Smith TR, Kumar V. Specific control of immunity by regulatory CD8 T cells. Cell Mol Immunol (2005) 2:11-19.
66. Kapp JA, Bucy RP. CD8+ suppressor T cells resurrected. Hum Immunol (2008) 69:715-20. doi:10.1016/j.humimm.2008.07.018
67. Cerf-Bensussan N, Jarry A, Brousse N, Lisowska-Grospierre B, Guy-Grand D, Griscelli C. A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. Eur J Immunol (1987) 17:1279-85. doi:10.1002/eji.1830170910
68. Cepek KL, Parker CM, Madara JL, Brenner MB. Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol (1993) 150:3459-70.
69. Chaput N, Louafi S, Bardier A, Charlotte F, Vaillant JC, Menegaux F, et al. Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue. Gut (2009) 58:520-9. doi:10.1136/gut.2008.158824
70. Nigam P, Velu V, Kannanganat S, Chennareddi L, Kwa S, Siddiqui M, et al. Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control. J Immunol (2010) 184:1690-701. doi:10.4049/jimmunol.0902955