Epithelial and dendritic cells in the thymic medulla promote cd4+foxp3+ regulatory t cell development via the cd27-cd70 pathway

Journal of Experimental Medicine

Volumn 210, Issue 4, 2013, Pages 715-728

  Coquet, Jonathan M ^a   Ribot, Julie C ^b   Ba̧bala, Nikolina ^a   Middendorp, Sabine ^a   van der Horst, Gerda ^a   Xiao, Yanling ^a   Neves, Joana F ^c,d   Fonseca Pereira, Diogo ^b   Jacobs, Heinz ^a   Pennington, Daniel J ^c   Silva Santos, Bruno ^b,e   Borst, Jannie ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^d UNIVERSITY OF COIMBRA   (Portugal)

^e INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

CD27 ANTIGEN; CD4 ANTIGEN; CD70 ANTIGEN; CD8ALPHA ANTIGEN; TRANSCRIPTION FACTOR FOXP3; AUTOIMMUNE REGULATOR PROTEIN; CD8 ANTIGEN; CD8 ANTIGEN, ALPHA CHAIN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; TRANSCRIPTION FACTOR;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL COUNT; CELL LINE; CELL MATURATION; CHIMERA; CONTROLLED STUDY; DENDRITIC CELL; EPITHELIUM CELL; IN VITRO STUDY; LYMPHOID ORGAN; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; THYMOCYTE; THYMUS; ALLOTRANSPLANTATION; ANIMAL; BONE MARROW TRANSPLANTATION; CELL SURVIVAL; CYTOLOGY; GENETICS; HISTOCOMPATIBILITY; IMMUNOLOGY; MOUSE MUTANT; PHYSIOLOGY; PRE T LYMPHOCYTE;

ANIMALS; ANTIGENS, CD27; ANTIGENS, CD70; ANTIGENS, CD8; BONE MARROW TRANSPLANTATION; CELL SURVIVAL; DENDRITIC CELLS; EPITHELIAL CELLS; FORKHEAD TRANSCRIPTION FACTORS; MICE; MICE, KNOCKOUT; PRECURSOR CELLS, T-LYMPHOID; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; THYMUS GLAND; TRANSCRIPTION FACTORS; TRANSPLANTATION CHIMERA; TRANSPLANTATION, HOMOLOGOUS;

MLCS; MLOWN;

EID: 84878646386     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20112061     Document Type: Article

References (76)

1. Acuto, O., and F. Michel. 2003. CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat. Rev. Immunol. 3:939-951. http://dx.doi.org/10.1038/nri1248
2. Anderson, M.S., E.S. Venanzi, L. Klein, Z. Chen, S.P. Berzins, S.J. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, and D. Mathis. 2002. Projection of an immunological self shadow within the thymus by the aire protein. Science. 298:1395-1401. http://dx.doi.org/10.1126/science.1075958
3. Apostolou, I., A. Sarukhan, L. Klein, and H. von Boehmer. 2002. Origin of regulatory T cells with known specificity for antigen. Nat. Immunol. 3:756-763.
4. + regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat. Immunol. 8:351- 358. http://dx.doi.org/10.1038/ni1444
5. Atarashi, K., T. Tanoue, T. Shima, A. Imaoka, T. Kuwahara, Y. Momose, G. Cheng, S. Yamasaki, T. Saito, Y. Ohba, et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 331: 337-341. http://dx.doi.org/10.1126/science.1198469
6. Bautista, J.L., C.W. Lio, S.K. Lathrop, K. Forbush, Y. Liang, J. Luo, A.Y. Rudensky, and C.S. Hsieh. 2009. Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat. Immunol. 10:610-617. http://dx.doi.org/10.1038/ni.1739
7. Bennett, C.L., J. Christie, F. Ramsdell, M.E. Brunkow, P.J. Ferguson, L. Whitesell, T.E. Kelly, F.T. Saulsbury, P.F. Chance, and H.D. Ochs. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27:20-21. http://dx.doi.org/10.1038/83713
8. Brunkow, M.E., E.W. Jeffery, K.A. Hjerrild, B. Paeper, L.B. Clark, S.A. Yasayko, J.E. Wilkinson, D. Galas, S.F. Ziegler, and F. Ramsdell. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27:68-73. http://dx.doi.org/10.1038/83784
9. + regulatory T cells. J. Immunol. 178:280-290.
10. Burchill, M.A., J. Yang, K.B. Vang, J.J. Moon, H.H. Chu, C.W. Lio, A.L. Vegoe, C.S. Hsieh, M.K. Jenkins, and M.A. Farrar. 2008. Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity. 28:112-121. http://dx.doi.org/10.1016/j.immuni.2007.11.022
11. Ciofani, M., and J.C. Zúñiga-Pflücker. 2010. Determining γδ versus αβ T cell development. Nat. Rev. Immunol. 10:657-663.
12. Claus, C., C. Riether, C. Schürch, M.S. Matter, T. Hilmenyuk, and A.F. Ochsenbein. 2012. CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer Res. 72:3664-3676. http://dx.doi.org/10.1158/0008-5472.CAN-11-2791
13. Coquet, J.M., S. Middendorp, G. van der Horst, J. Kind, E.A.M. Veraar, Y. Xiao, H. Jacobs, and J. Borst. 2013. The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity. Immunity. 38:53-65. http://dx.doi.org/10.1016/j.immuni.2012.09.009
14. Derbinski, J., J. Gäbler, B. Brors, S. Tierling, S. Jonnakuty, M. Hergenhahn, L. Peltonen, J. Walter, and B. Kyewski. 2005. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J. Exp. Med. 202:33-45. http://dx.doi.org/10.1084/jem.20050471
15. Dorner, B.G., M.B. Dorner, X. Zhou, C. Opitz, A. Mora, S. Güttler, A. Hutloff, H.W. Mages, K. Ranke, M. Schaefer, et al. 2009. Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells. Immunity. 31:823-833. http://dx.doi.org/10.1016/j.immuni.2009.08.027
16. Eldering, E., C.A. Spek, H.L. Aberson, A. Grummels, I.A. Derks, A.F. de Vos, C.J. McElgunn, and J.P. Schouten. 2003. Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Nucleic Acids Res. 31:e153. http://dx.doi.org/10.1093/nar/gng153
17. +CD25+ regulatory T cells. Nat. Immunol. 4:330-336. http://dx.doi.org/10.1038/ni904
18. Fontenot, J.D., J.L. Dooley, A.G. Farr, and A.Y. Rudensky. 2005a. Developmental regulation of Foxp3 expression during ontogeny. J. Exp. Med. 202:901-906. http://dx.doi.org/10.1084/jem.20050784
19. Fontenot, J.D., J.P. Rasmussen, M.A. Gavin, and A.Y. Rudensky. 2005b. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 6:1142-1151. http://dx.doi.org/10.1038/ni1263
20. Gallegos, A.M., and M.J. Bevan. 2004. Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J. Exp. Med. 200:1039-1049. http://dx.doi.org/10.1084/jem.20041457
21. Gravestein, L.A., W. van Ewijk, F. Ossendorp, and J. Borst. 1996. CD27 cooperates with the pre-T cell receptor in the regulation of murine T cell development. J. Exp. Med. 184:675-685. http://dx.doi.org/10.1084/jem.184.2.675
22. Gray, D., J. Abramson, C. Benoist, and D. Mathis. 2007. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J. Exp. Med. 204:2521-2528. http://dx.doi.org/10.1084/jem.20070795
23. Hendriks, J., L.A. Gravestein, K. Tesselaar, R.A. van Lier, T.N. Schumacher, and J. Borst. 2000. CD27 is required for generation and long-term maintenance of T cell immunity. Nat. Immunol. 1:433-440. http://dx.doi.org/10.1038/80877
24. Hendriks, J., Y. Xiao, and J. Borst. 2003. CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J. Exp. Med. 198:1369-1380. http://dx.doi.org/10.1084/jem.20030916
25. Hendriks, J., Y. Xiao, J.W. Rossen, K.F. van der Sluijs, K. Sugamura, N. Ishii, and J. Borst. 2005. During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion. J. Immunol. 175:1665-1676.
26. Hintzen, R.Q., S.M. Lens, G. Koopman, S.T. Pals, H. Spits, and R.A. van Lier. 1994. CD70 represents the human ligand for CD27. Int. Immunol. 6:477-480. http://dx.doi.org/10.1093/intimm/6.3.477
27. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science. 299:1057-1061. http://dx.doi.org/10.1126/science.1079490
28. Hsieh, C.S., Y. Zheng, Y. Liang, J.D. Fontenot, and A.Y. Rudensky. 2006. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7:401-410. http://dx.doi.org/10.1038/ni1318
29. Igarashi, H., S.C. Gregory, T. Yokota, N. Sakaguchi, and P.W. Kincade. 2002. Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity. 17:117-130. http://dx.doi.org/10.1016/S1074-7613(02)00366-7
30. Jiang, W., W.J. Swiggard, C. Heufler, M. Peng, A. Mirza, R.M. Steinman, and M.C. Nussenzweig. 1995. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature. 375:151-155. http://dx.doi.org/10.1038/375151a0
31. +CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2:301-306. http://dx.doi.org/10.1038/86302
32. Kawahata, K., Y. Misaki, M. Yamauchi, S. Tsunekawa, K. Setoguchi, J. Miyazaki, and K. Yamamoto. 2002. Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J. Immunol. 168:4399-4405.
33. Keller, A.M., T.A. Groothuis, E.A. Veraar, M. Marsman, L. Maillette de Buy Wenniger, H. Janssen, J. Neefjes, and J. Borst. 2007. Costimulatory ligand CD70 is delivered to the immunological synapse by shared intracellular trafficking with MHC class II molecules. Proc. Natl. Acad. Sci. USA. 104:5989-5994. http://dx.doi.org/10.1073/pnas.0700946104
34. +CD25+ T regulatory cells. Nat. Immunol. 4:337- 342. http://dx.doi.org/10.1038/ni909
35. Kumanogoh, A., X. Wang, I. Lee, C. Watanabe, M. Kamanaka, W. Shi, K. Yoshida, T. Sato, S. Habu, M. Itoh, et al. 2001. Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J. Immunol. 166:353-360.
36. Lei, Y., A.M. Ripen, N. Ishimaru, I. Ohigashi, T. Nagasawa, L.T. Jeker, M.R. Bösl, G.A. Holländer, Y. Hayashi, Rde.W. Malefyt, et al. 2011. Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development. J. Exp. Med. 208:383-394. http://dx.doi.org/10.1084/jem.20102327
37. Li, J., J. Park, D. Foss, and I. Goldschneider. 2009. Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus. J. Exp. Med. 206:607-622. http://dx.doi.org/10.1084/jem.20082232
38. Lio, C.W., and C.S. Hsieh. 2008. A two-step process for thymic regulatory T cell development. Immunity. 28:100-111. http://dx.doi.org/10.1016/j.immuni.2007.11.021
39. Lio, C.W., L.F. Dodson, C.M. Deppong, C.S. Hsieh, and J.M. Green. 2010. CD28 facilitates the generation of Foxp3(-) cytokine responsive regulatory T cell precursors. J. Immunol. 184:6007-6013. http://dx.doi. org/10.4049/jimmunol.1000019
40. Liston, A., and A.Y. Rudensky. 2007. Thymic development and peripheral homeostasis of regulatory T cells. Curr. Opin. Immunol. 19:176-185. http://dx.doi.org/10.1016/j.coi.2007.02.005
41. + T cells in the thymic cortex. Proc. Natl. Acad. Sci. USA. 105:11903-11908. http://dx.doi.org/10.1073/pnas.0801506105
42. Liu, Y.J. 2006. A unified theory of central tolerance in the thymus. Trends Immunol. 27:215-221. http://dx.doi.org/10.1016/j.it.2006.03.004
43. Lomada, D., B. Liu, L. Coghlan, Y. Hu, and E.R. Richie. 2007. Thymus medulla formation and central tolerance are restored in IKKalpha-/- mice that express an IKKalpha transgene in keratin 5+ thymic epithelial cells. J. Immunol. 178:829-837.
44. Luther, S.A., and H. Acha-Orbea. 1997. Mouse mammary tumor virus: immunological interplays between virus and host. Adv. Immunol. 65:139- 243. http://dx.doi.org/10.1016/S0065-2776(08)60743-9
45. Martorell, J., I. Rojo, R. Vilella, E. Martinez-Caceres, and J. Vives. 1990. CD27 induction on thymocytes. J. Immunol. 145:1356-1363.
46. McKean, D.J., C.J. Huntoon, M.P. Bell, X. Tai, S. Sharrow, K.E. Hedin, A. Conley, and A. Singer. 2001. Maturation versus death of developing double-positive thymocytes reflects competing effects on Bcl-2 expression and can be regulated by the intensity of CD28 costimulation. J. Immunol. 166:3468-3475.
47. Nolte, M.A., R.W. van Olffen, K.P. van Gisbergen, and R.A. van Lier. 2009. Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology. Immunol. Rev. 229:216-231. http://dx.doi.org/10.1111/j.1600-065X.2009.00774.x
48. + CD8+ stage but requires early T-cell receptor expression. Immunol. Cell Biol. 88:523-528. http://dx.doi.org/10.1038/icb.2010.4
49. Oshima, H., H. Nakano, C. Nohara, T. Kobata, A. Nakajima, N.A. Jenkins, D.J. Gilbert, N.G. Copeland, T. Muto, H. Yagita, and K. Okumura. 1998. Characterization of murine CD70 by molecular cloning and mAb. Int. Immunol. 10:517-526. http://dx.doi.org/10.1093/intimm/10.4.517
50. Ouyang, W., O. Beckett, Q. Ma, and M.O. Li. 2010. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity. 32:642-653. http://dx.doi.org/10.1016/j.immuni.2010.04.012
51. +CD25+ T cells. Immunity. 25:249-259. http://dx.doi.org/10.1016/j.immuni.2006.05.016
52. Peperzak, V., E.A. Veraar, A.M. Keller, Y. Xiao, and J. Borst. 2010a. The Pim kinase pathway contributes to survival signaling in primed CD8+ T cells upon CD27 costimulation. J. Immunol. 185:6670-6678. http://dx.doi.org/10.4049/jimmunol.1000159
53. Peperzak, V., Y. Xiao, E.A. Veraar, and J. Borst. 2010b. CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production. J. Clin. Invest. 120:168-178. http://dx.doi.org/10.1172/JCI40178
54. Proietto, A.I., S. van Dommelen, P. Zhou, A. Rizzitelli, A. D'Amico, R.J. Steptoe, S.H. Naik, M.H. Lahoud, Y. Liu, P. Zheng, et al. 2008. Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc. Natl. Acad. Sci. USA. 105:19869-19874. http://dx.doi.org/10.1073/pnas.0810268105
55. Ribot, J., P. Romagnoli, and J.P. van Meerwijk. 2006. Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR repertoire. J. Immunol. 177:1101-1107.
56. Ribot, J.C., A. deBarros, D.J. Pang, J.F. Neves, V. Peperzak, S.J. Roberts, M. Girardi, J. Borst, A.C. Hayday, D.J. Pennington, and B. Silva-Santos. 2009. CD27 is a thymic determinant of the balance between interferon-gammaand interleukin 17-producing gammadelta T cell subsets. Nat. Immunol. 10:427-436. http://dx.doi.org/10.1038/ni.1717
57. Romagnoli, P., D. Hudrisier, and J.P. van Meerwijk. 2002. Preferential recognition of self antigens despite normal thymic deletion of CD4(+)CD25(+) regulatory T cells. J. Immunol. 168:1644-1648.
58. Román, E., H. Shino, F.X. Qin, and Y.J. Liu. 2010. Cutting edge: Hematopoietic-derived APCs select regulatory T cells in thymus. J. Immunol. 185:3819-3823. http://dx.doi.org/10.4049/jimmunol.0900665
59. Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155: 1151-1164.
60. Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. Regulatory T cells and immune tolerance. Cell. 133:775-787. http://dx.doi.org/10.1016/j.cell.2008.05.009
61. Sanchez, P.J., J.A. McWilliams, C. Haluszczak, H. Yagita, and R.M. Kedl. 2007. Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo. J. Immunol. 178:1564-1572.
62. + T regulatory cell-mediated suppression. Immunity. 30:636-645. http://dx.doi.org/10.1016/j.immuni.2009.04.010
63. + T cells to produce IFN-γ by an IL-12-independent but CD70-dependent mechanism in vivo. J. Exp. Med. 204:1095-1106. http://dx.doi.org/10.1084/jem.20070176
64. + regulatory T cells promiscuously accept thymic signals critical for their development. Proc. Natl. Acad. Sci. USA. 105:973-978. http://dx.doi.org/10.1073/pnas.0709071105
65. Tai, X., M. Cowan, L. Feigenbaum, and A. Singer. 2005. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat. Immunol. 6:152-162. http://dx.doi.org/10.1038/ni1160
66. Taylor, S.R., D.R. Alexander, J.C. Cooper, C.F. Higgins, and J.I. Elliott. 2007. Regulatory T cells are resistant to apoptosis via TCR but not P2X7. J. Immunol. 178:3474-3482.
67. Tesselaar, K., Y. Xiao, R. Arens, G.M. van Schijndel, D.H. Schuurhuis, R.E. Mebius, J. Borst, and R.A. van Lier. 2003. Expression of the murine CD27 ligand CD70 in vitro and in vivo. J. Immunol. 170:33-40.
68. van Ewijk, W., Y. Ron, J. Monaco, J. Kappler, P. Marrack, M. Le Meur, P. Gerlinger, B. Durand, C. Benoist, and D. Mathis. 1988. Compartmentalization of MHC class II gene expression in transgenic mice. Cell. 53:357-370. http://dx.doi.org/10.1016/0092-8674(88)90156-0
69. van Santen, H.M., C. Benoist, and D. Mathis. 2004. Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells. J. Exp. Med. 200:1221-1230. http://dx.doi.org/10.1084/jem.20041022
70. Van Vliet, E., M. Melis, and W. Van Ewijk. 1984. Monoclonal antibodies to stromal cell types of the mouse thymus. Eur. J. Immunol. 14:524-529. http://dx.doi.org/10.1002/eji.1830140608
71. Vang, K.B., J. Yang, A.J. Pagán, L.X. Li, J. Wang, J.M. Green, A.A. Beg, and M.A. Farrar. 2010. Cutting edge: CD28 and c-Rel-dependent pathways initiate regulatory T cell development. J. Immunol. 184:4074- 4077. http://dx.doi.org/10.4049/jimmunol.0903933
72. von Boehmer, H. 2004. Selection of the T-cell repertoire: receptor-controlled checkpoints in T-cell development. Adv. Immunol. 84:201-238. http://dx.doi.org/10.1016/S0065-2776(04)84006-9
73. +CD25+ regulatory T cells in human thymus. Nature. 436:1181- 1185. http://dx.doi.org/10.1038/nature03886
74. Wildin, R.S., F. Ramsdell, J. Peake, F. Faravelli, J.L. Casanova, N. Buist, E. Levy-Lahad, M. Mazzella, O. Goulet, L. Perroni, et al. 2001. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27:18-20. http://dx.doi.org/10.1038/83707
75. + T cells to provide help for the memory CD8+ T cell response after protein immunization. J. Immunol. 181:1071-1082.
76. Yano, M., N. Kuroda, H. Han, M. Meguro-Horike, Y. Nishikawa, H. Kiyonari, K. Maemura, Y. Yanagawa, K. Obata, S. Takahashi, et al. 2008. Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance. J. Exp. Med. 205:2827-2838. http://dx.doi.org/10.1084/jem.20080046