Affinity for self antigen selects Treg cells with distinct functional properties

Nature Immunology

Volumn 17, Issue 9, 2016, Pages 1093-1101

  Wyss, Lena ^a   Stadinski, Brian D ^b   King, Carolyn G ^a   Schallenberg, Sonja ^c   Mccarthy, Nicholas I ^d   Lee, Jun Young ^e,f   Kretschmer, Karsten ^c,g   Terracciano, Luigi M ^h   Anderson, Graham ^d   Surh, Charles D ^e,f,i   Huseby, Eric S ^b   Palmer, Ed ^a  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^c CENTER FOR REGENERATIVE THERAPIES DRESDEN   (Germany)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^e Institute for Basic Science   (South Korea)

^f Pohang University of Science and Technology (POSTECH)   (South Korea)

^g GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

^h UNIVERSITY HOSPITAL BASEL   (Switzerland)

ⁱ LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; SELF ANTIGEN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; AUTOANTIGEN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; TNFRSF18 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL INFILTRATION; CELL POPULATION; CELL PROLIFERATION; CELL SELECTION; CELL SURFACE; COLITIS; FEMALE; FLOW CYTOMETRY; HOMEOSTASIS; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; THYMOCYTE; WASTING SYNDROME; ANIMAL; ANTIGEN MEDIATED CLONAL SELECTION; AUTOIMMUNITY; C57BL MOUSE; CELL CULTURE; DISEASE MODEL; GENETICS; HUMAN; IMMUNOLOGY; KNOCKOUT MOUSE; LYMPH NODE; METABOLISM; T LYMPHOCYTE SUBPOPULATION; TRANSPLANTATION;

ANIMALS; AUTOANTIGENS; AUTOIMMUNITY; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLS, CULTURED; CLONAL SELECTION, ANTIGEN-MEDIATED; COLITIS; DISEASE MODELS, ANIMAL; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN; HOMEOSTASIS; HUMANS; LYMPH NODES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; RECEPTORS, ANTIGEN, T-CELL; T-CELL ANTIGEN RECEPTOR SPECIFICITY; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; WASTING SYNDROME;

EID: 84980340465     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3522     Document Type: Article

References (63)

1. Fontenot, J.D., Gavin, M.A., & Rudensky, A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330-336 (2003
2. Khattri, R., Cox, T., Yasayko, S.A., & Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4, 337-342 (2003
3. Hori, S., Nomura, T., & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061 (2003
4. Bennett, C.L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20-21 (2001
5. Josefowicz, S.Z., Lu, L.F., & Rudensky, A.Y. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531-564 (2012
6. Ohkura, N., Kitagawa, Y., & Sakaguchi, S. Development and maintenance of regulatory T cells. Immunity 38, 414-423 (2013
7. Harrison, O.J., & Powrie, F.M. Regulatory T cells and immune tolerance in the intestine. Cold Spring Harb. Perspect. Biol. 5, 5 (2013
8. Jordan, M.S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2, 301-306 (2001
9. Apostolou, I., Sarukhan, A., Klein, L., & von Boehmer, H. Origin of regulatory T cells with known specificity for antigen. Nat. Immunol. 3, 756-763 (2002
10. Klein, L., & Jovanovic, K. Regulatory T cell differentiation: turning harmful into useful. Immunity 37, 441-443 (2012
11. Chen, W. et al. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886 (2003
12. Zheng, Y. et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808-812 (2010
13. Samstein, R.M., Josefowicz, S.Z., Arvey, A., Treuting, P.M., & Rudensky, A.Y. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell 150, 29-38 (2012
14. Yadav, M. et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets. in vivo. J Exp Med 209, 1713-1722 (2012
15. Haribhai, D. et al. A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 35, 109-122 (2011
16. Smigiel, K.S. et al. CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. J. Exp. Med. 211, 121-136 (2014
17. Huehn, J. et al. Developmental stage, phenotype, and migration distinguish naive-And effector/memory-like CD4+ regulatory T cells. J. Exp. Med. 199, 303-313 (2004
18. Miyara, M. et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30, 899-911 (2009
19. Levine, A.G., Arvey, A., Jin, W., & Rudensky, A.Y. Continuous requirement for the TCR in regulatory T cell function. Nat. Immunol. 15, 1070-1078 (2014
20. Schmidt, A.M. et al. Regulatory T cells require TCR signaling for their suppressive function. J. Immunol. 194, 4362-4370 (2015
21. Hsieh, C.S., Zheng, Y., Liang, Y., Fontenot, J.D., & Rudensky, A.Y. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7, 401-410 (2006
22. Lee, H.-M., Bautista, J.L., Scott-Browne, J., Mohan, J.F., & Hsieh, C.-S. A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self. Immunity 37, 475-486 (2012
23. Pacholczyk, R. et al. Nonself-Antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity 27, 493-504 (2007
24. Hsieh, C.S. et al. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 21, 267-277 (2004
25. Pacholczyk, R., Ignatowicz, H., Kraj, P., & Ignatowicz, L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity 25, 249-259 (2006
26. Lathrop, S.K. et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 478, 250-254 (2011
27. Yadav, M., Stephan, S., & Bluestone, J.A. Peripherally induced Tregs: role in immune homeostasis and autoimmunity. Front. Immunol. 4, 232 (2013
28. Yang, E., Zou, T., Leichner, T.M., Zhang, S.L., & Kambayashi, T. Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus. Eur. J. Immunol. 44, 2712-2720 (2014
29. Cowan, J.E., McCarthy, N.I., & Anderson, G. CCR7 controls thymus recirculation, but not production and emigration, of Foxp3(+) T cells. Cell Rep. 14, 1041-1048 (2016
30. Kim, K.S. et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351, 858-863 (2016
31. Moran, A.E. et al. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208, 1279-1289 (2011
32. Mandl, J.N., Monteiro, J.P., Vrisekoop, N., & Germain, R.N. T cell-positive selection uses self-ligand binding strength to optimize repertoire recognition of foreign antigens. Immunity 38, 263-274 (2013
33. Kuczma, M. et al. Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset. J. Immunol. 183, 3731-3741 (2009
34. Lin, W. et al. Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 8, 359-368 (2007
35. Wagner, N. et al. Critical role for beta7 integrins in formation of the gut-Associated lymphoid tissue. Nature 382, 366-370 (1996
36. Killebrew, J.R. et al. A self-reactive TCR drives the development of Foxp3+ regulatory T cells that prevent autoimmune disease. J. Immunol. 187, 861-869 (2011
37. Thornton, A.M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433-3441 (2010
38. Weiss, J.M. et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med 209, 1723-1742 (2012
39. Kim, J.M., Rasmussen, J.P., & Rudensky, A.Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191-197 (2007
40. Morelli, A.E., & Thomson, A.W. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7, 610-621 (2007
41. Liu, K. et al. In vivo analysis of dendritic cell development and homeostasis. Science 324, 392-397 (2009
42. Tadokoro, C.E. et al. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 203, 505-511 (2006
43. Mottet, C., Uhlig, H.H., & Powrie, F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J. Immunol. 170, 3939-3943 (2003
44. Round, J.L., & Mazmanian, S.K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. Sci. USA 107, 12204-12209 (2010
45. Haribhai, D. et al. Alternatively activated macrophages boost induced regulatory T and Th17 cell responses during immunotherapy for colitis. J. Immunol. 196, 3305-3317 (2016
46. Sharma, R., Sung, S.S., Gaskin, F., Fu, S.M., & Ju, S.T. A novel function of IL-2: chemokine/chemoattractant/retention receptor genes induction in Th subsets for skin and lung inflammation. J. Autoimmun. 38, 322-331 (2012
47. Zelante, T., Fric, J., Wong, A.Y., & Ricciardi-Castagnoli, P. Interleukin-2 production by dendritic cells and its immuno-regulatory functions. Front. Immunol. 3, 161 (2012
48. Kurts, C. et al. CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-Antigens and favors autoimmunity. J. Exp. Med. 186, 2057-2062 (1997
49. Koehli, S., Naeher, D., Galati-Fournier, V., Zehn, D., & Palmer, E. Optimal T-cell receptor affinity for inducing autoimmunity. Proc. Natl. Acad. Sci. USA 111, 17248-17253 (2014
50. Barnden, M.J., Allison, J., Heath, W.R., & Carbone, F.R. Defective TCR expression in transgenic mice constructed using cDNA-based alpha-And beta-chain genes under the control of heterologous regulatory elements. Immunol. Cell Biol. 76, 34-40 (1998
51. Lin, W. et al. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J. Allergy Clin. Immunol. 116, 1106-1115 (2005
52. Huseby, E.S. et al. How the T cell repertoire becomes peptide and MHC specific. Cell 122, 247-260 (2005
53. Malissen, M. et al. Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene. EMBO J. 14, 4641-4653 (1995
54. Wang, Y. et al. Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells. J. Immunol. 180, 1565-1575 (2008
55. Zehn, D., & Bevan, M.J. T cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause autoimmunity. Immunity 25, 261-270 (2006
56. Stadinski, B.D. et al. A role for differential variable gene pairing in creating T cell receptors specific for unique major histocompatibility ligands. Immunity 35, 694-704 (2011
57. Vanguri, V., Govern, C.C., Smith, R., & Huseby, E.S. Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection. Proc. Natl. Acad. Sci. USA 110, 288-293 (2013
58. White, A., Jenkinson, E., & Anderson, G. Reaggregate thymus cultures. J. Vis. Exp. 18, 905 (2008
59. Aronesty, E. ea-utils: "Command-line tools for processing biological sequencing data". 2011 [cited]Available from: http://code.google.com/p/ea-utils
60. Yang, X. et al. TCRklass: a new K-string-based algorithm for human and mouse TCR repertoire characterization. J. Immunol. 194, 446-454 (2015
61. Colwell, F.S. et al. Estimates of biogenic methane production rates in deep marine sediments at Hydrate Ridge, Cascadia margin. Appl. Environ. Microbiol. 74, 3444-3452 (2008
62. Shannon, C.E. A mathematical theory of communication. Bell Syst. Tech. J. 27, 379-423 (1948
63. Simpson, E.H. Measurement of diversity. Nature 163, 688-688 (1949