Differential response of regulatory and conventional CD4+ lymphocytes to CD3 engagement: Clues to a possible mechanism of anti-CD3 action?

Journal of Immunology

Volumn 191, Issue 7, 2013, Pages 3694-3704

  Li, Li ^a   Nishio, Junko ^a   Van Maurik, André ^b   Mathis, Diane ^a   Benoist, Christophe ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIBODY; CD3 ANTIGEN; CD4 ANTIGEN; INHIBITOR OF DIFFERENTIATION 2; INHIBITOR OF DIFFERENTIATION 3; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; MONOCLONAL ANTIBODY CD3; PROTEIN GFI1; RECOMBINANT INTERLEUKIN 7; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD4+ T LYMPHOCYTE; CELLULAR IMMUNITY; DIABETES MELLITUS; DRUG POTENTIATION; HUMAN; HUMAN CELL; IMMUNOREGULATION; LYMPHOCYTE DIFFERENTIATION; MALE; MOLECULAR MECHANICS; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REMISSION; TRANSCRIPTION REGULATION; UPREGULATION;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD3; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; DRUG SYNERGISM; GENE EXPRESSION REGULATION; HUMANS; INTERLEUKIN-7; MICE; MICE, TRANSGENIC; PROTEIN BINDING; RECEPTORS, INTERLEUKIN-7; T-LYMPHOCYTES, REGULATORY;

EID: 84885093230     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1300408     Document Type: Article

References (65)

1. Herold, K. C., J. A. Bluestone, A. G. Montag, A. Parihar, A. Wiegner, R. E. Gress, and R. Hirsch. 1992. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes 41:385-391.
2. Vallera, D. A., S. F. Carroll, S. Brief, and B. R. Blazar. 1992. Anti-CD3 immunotoxin prevents low-dose STZ/interferon-induced autoimmune diabetes in mouse. Diabetes 41:457-464.
3. Hayward, A. R., and M. Shriber. 1992. Reduced incidence of insulitis in NOD mice following anti-CD3 injection: requirement for neonatal injection. J. Autoimmun. 5:59-67.
4. Chatenoud, L., E. Thervet, J. Primo, and J. F. Bach. 1994. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc. Natl. Acad. Sci. USA 91:123-127.
5. Keymeulen, B., E. Vandemeulebroucke, A. G. Ziegler, C. Mathieu, L. Kaufman, G. Hale, F. Gorus, M. Goldman, M. Walter, S. Candon, et al. 2005. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N. Engl. J. Med. 352:2598-2608.
6. Herold, K. C., W. Hagopian, J. A. Auger, E. Poumian-Ruiz, L. Taylor, D. Donaldson, S. E. Gitelman, D. M. Harlan, D. Xu, R. A. Zivin, and J. A. Bluestone. 2002. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N. Engl. J. Med. 346:1692-1698.
7. Keymeulen, B., M. Walter, C. Mathieu, L. Kaufman, F. Gorus, R. Hilbrands, E. Vandemeulebroucke, U. Van de Velde, L. Crenier, C. De Block, et al. 2010. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia 53:614-623.
8. Herold, K. C., S. Gitelman, C. Greenbaum, J. Puck, W. Hagopian, P. Gottlieb, P. Sayre, P. Bianchine, E. Wong, V. Seyfert-Margolis, et al; Immune Tolerance Network ITN007AI Study Group. 2009. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin. Immunol. 132:166-173.
9. Sherry, N., W. Hagopian, J. Ludvigsson, S. M. Jain, J. Wahlen, R. J. Ferry, Jr., B. Bode, S. Aronoff, C. Holland, D. Carlin, et al; Protégé Trial Investigators. 2011. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet 378:487-497.
10. GlaxoSmithKline. Press release. GlaxoSmithKline and Tolerx announce phase III DEFEND-1 study of otelixizumab in type 1 diabetes did not meet its primary endpoint. Available at: http://us.gsk.com/html/media-news/pressreleases/2011/ 2011-pressrelease-10039.htm. Accessed: August 13, 2013.
11. Bach, J. F. 2011. Anti-CD3 antibodies for type 1 diabetes: beyond expectations. Lancet 378:459-460.
12. Herold, K. C., S. E. Gitelman, U. Masharani, W. Hagopian, B. Bisikirska, D. Donaldson, K. Rother, B. Diamond, D. M. Harlan, and J. A. Bluestone. 2005. A single course of anti-CD3 monoclonal antibody hOKT3gamma1 (Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 54:1763-1769.
13. Waldron-Lynch, F., O. Henegariu, S. Deng, P. Preston-Hurlburt, J. Tooley, R. Flavell, and K. C. Herold. 2012. Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients. Sci Transl. Med 4:118ra12.
14. Kohm, A. P., J. S. Williams, A. L. Bickford, J. S. McMahon, L. Chatenoud, J. F. Bach, J. A. Bluestone, and S. D. Miller. 2005. Treatment with nonmitogenic anti-CD3 monoclonal antibody induces CD4+ T cell unresponsiveness and functional reversal of established experimental autoimmune encephalomyelitis. J. Immunol. 174:4525-4534.
15. Alegre, M. L., J. Y. Tso, H. A. Sattar, J. Smith, F. Desalle, M. Cole, and J. A. Bluestone. 1995. An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity. J. Immunol. 155:1544-1555.
16. Smith, J. A., J. Y. Tso, M. R. Clark, M. S. Cole, and J. A. Bluestone. 1997. Nonmitogenic anti-CD3 monoclonal antibodies deliver a partial T cell receptor signal and induce clonal anergy. J. Exp. Med. 185:1413-1422.
17. Penaranda, C., Q. Tang, and J. A. Bluestone. 2011. Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells. J. Immunol. 187:2015-2022.
18. Chatenoud, L., J. Primo, and J. F. Bach. 1997. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J. Immunol. 158:2947-2954.
19. You, S., B. Leforban, C. Garcia, J. F. Bach, J. A. Bluestone, and L. Chatenoud. 2007. Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc. Natl. Acad. Sci. USA 104:6335-6340.
20. Belghith, M., J. A. Bluestone, S. Barriot, J. Mégret, J. F. Bach, and L. Chatenoud. 2003. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat. Med. 9:1202-1208.
21. Bresson, D., L. Togher, E. Rodrigo, Y. Chen, J. A. Bluestone, K. C. Herold, and M. von Herrath. 2006. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J. Clin. Invest. 116:1371-1381.
22. Nishio, J., M. Feuerer, J. Wong, D. Mathis, and C. Benoist. 2010. Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified peripheral niche constraints. J. Exp. Med. 207:1879-1889.
23. Josefowicz, S. Z., L. F. Lu, and A. Y. Rudensky. 2012. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30:531-564.
24. Vignali, D. A., L. W. Collison, and C. J. Workman. 2008. How regulatory T cells work. Nat. Rev. Immunol. 8:523-532.
25. Feuerer, M., J. A. Hill, D. Mathis, and C. Benoist. 2009. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat. Immunol. 10:689-695.
26. Salomon, B., D. J. Lenschow, L. Rhee, N. Ashourian, B. Singh, A. Sharpe, and J. A. Bluestone. 2000. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12:431-440.
27. Feuerer, M., Y. Shen, D. R. Littman, C. Benoist, and D. Mathis. 2009. How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity 31:654-664.
28. Chen, Z., A. E. Herman, M. Matos, D. Mathis, and C. Benoist. 2005. Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J. Exp. Med. 202:1387-1397.
29. Tarbell, K. V., S. Yamazaki, K. Olson, P. Toy, and R. M. Steinman. 2004. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199:1467-1477.
30. Chen, G., G. Han, J. Wang, R. Wang, R. Xu, B. Shen, J. Qian, and Y. Li. 2008. Essential roles of TGF-beta in anti-CD3 antibody therapy: reversal of diabetes in nonobese diabetic mice independent of Foxp3+CD4+ regulatory T cells. J. Leukoc. Biol. 83:280-287.
31. Bettelli, E., Y. Carrier, W. Gao, T. Korn, T. B. Strom, M. Oukka, H. L. Weiner, and V. K. Kuchroo. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235-238.
32. Darce, J., D. Rudra, L. Li, J. Nishio, D. Cipolletta, A. Y. Rudensky, D. Mathis, and C. Benoist. 2012. An N-terminal mutation of the Foxp3 transcription factor alleviates arthritis but exacerbates diabetes. Immunity 36:731-741.
33. Mottram, P. L., L. J. Murray-Segal, W. Han, J. Maguire, and A. N. Stein-Oakley. 2002. Remission and pancreas isograft survival in recent onset diabetic NOD mice after treatment with low-dose anti-CD3 monoclonal antibodies. Transpl. Immunol. 10:63-72.
34. Obst, R., H. M. van Santen, R. Melamed, A. O. Kamphorst, C. Benoist, and D. Mathis. 2007. Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation. Proc. Natl. Acad. Sci. USA 104:15460-15465.
35. Hill, J. A., M. Feuerer, K. Tash, S. Haxhinasto, J. Perez, R. Melamed, D. Mathis, and C. Benoist. 2007. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27:786-800.
36. Ma, A., R. Koka, and P. Burkett. 2006. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu. Rev. Immunol. 24:657-679.
37. Liu, W., A. L. Putnam, Z. Xu-Yu, G. L. Szot, M. R. Lee, S. Zhu, P. A. Gottlieb, P. Kapranov, T. R. Gingeras, B. Fazekas de St Groth, et al. 2006. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 203:1701-1711.
38. Xue, H. H., P. E. Kovanen, C. A. Pise-Masison, M. Berg, M. F. Radovich, J. N. Brady, and W. J. Leonard. 2002. IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes. Proc. Natl. Acad. Sci. USA 99:13759-13764.
39. Swainson, L., E. Verhoeyen, F. L. Cosset, and N. Taylor. 2006. IL-7R alpha gene expression is inversely correlated with cell cycle progression in IL-7-stimulated T lymphocytes. J. Immunol. 176:6702-6708.
40. Alves, N. L., E. M. van Leeuwen, I. A. Derks, and R. A. van Lier. 2008. Differential regulation of human IL-7 receptor alpha expression by IL-7 and TCR signaling. J. Immunol. 180:5201-5210.
41. Simonetta, F., A. Chiali, C. Cordier, A. Urrutia, I. Girault, S. Bloquet, C. Tanchot, and C. Bourgeois. 2010. Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells. Eur. J. Immunol. 40:2528-2538.
42. Boyman, O., C. Ramsey, D. M. Kim, J. Sprent, and C. D. Surh. 2008. IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T cell expansion without lymphopenia. J. Immunol. 180:7265-7275.
43. André, I., A. Gonzalez, B. Wang, J. Katz, C. Benoist, and D. Mathis. 1996. Checkpoints in the progression of autoimmune disease: lessons from diabetes models. Proc. Natl. Acad. Sci. USA 93:2260-2263.
44. Tax, W. J., H. W. Willems, P. P. Reekers, P. J. Capel, and R. A. Koene. 1983. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature 304:445-447.
45. Crellin, N. K., R. V. Garcia, and M. K. Levings. 2007. Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood 109:2014-2022.
46. Zanin-Zhorov, A., Y. Ding, S. Kumari, M. Attur, K. L. Hippen, M. Brown, B. R. Blazar, S. B. Abramson, J. J. Lafaille, and M. L. Dustin. 2010. Protein kinase C-theta mediates negative feedback on regulatory T cell function. Science 328:372-376.
47. Zanin-Zhorov, A., J. Lin, J. Scher, S. Kumari, D. Blair, K. L. Hippen, B. R. Blazar, S. B. Abramson, J. J. Lafaille, and M. L. Dustin. 2012. Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function. Proc. Natl. Acad. Sci. USA 109:1625-1630.
48. Au-Yeung, B. B., S. E. Levin, C. Zhang, L. Y. Hsu, D. A. Cheng, N. Killeen, K. M. Shokat, and A. Weiss. 2010. A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity. Nat. Immunol. 11:1085-1092.
49. Bayer, A. L., J. Y. Lee, A. de la Barrera, C. D. Surh, and T. R. Malek. 2008. A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells. J. Immunol. 181:225-234.
50. Harnaha, J., J. Machen, M. Wright, R. Lakomy, A. Styche, M. Trucco, S. Makaroun, and N. Giannoukakis. 2006. Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes 55:158-170.
51. Gratz, I. K., H. A. Truong, S. H. Yang, M. M. Maurano, K. Lee, A. K. Abbas, and M. D. Rosenblum. 2013. Cutting Edge: memory regulatory t cells require IL-7 and not IL-2 for their maintenance in peripheral tissues. J. Immunol. 190:4483-4487.
52. Kim, G. Y., D. L. Ligons, C. Hong, M. A. Luckey, H. R. Keller, X. Tai, P. J. Lucas, R. E. Gress, and J. H. Park. 2012. An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis. J. Immunol. 188:5859-5866.
53. Mazzucchelli, R., J. A. Hixon, R. Spolski, X. Chen, W. Q. Li, V. L. Hall, J. Willette-Brown, A. A. Hurwitz, W. J. Leonard, and S. K. Durum. 2008. Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLP. Blood 112:3283-3292.
54. Di Caro, V., A. D'Anneo, B. Phillips, C. Engman, J. Harnaha, R. Lakomy, A. Styche, M. Trucco, and N. Giannoukakis. 2011. Interleukin-7 matures suppressive CD127 (+) forkhead box P3 (FoxP3) (+) T cells into CD127 (-) CD25 (high) FoxP3 (+) regulatory T cells. Clin. Exp. Immunol. 165:60-76.
55. Xue, H. H., J. Bollenbacher, V. Rovella, R. Tripuraneni, Y. B. Du, C. Y. Liu, A. Williams, J. P. McCoy, and W. J. Leonard. 2004. GA binding protein regulates interleukin 7 receptor alpha-chain gene expression in T cells. Nat. Immunol. 5:1036-1044.
56. Chandele, A., N. S. Joshi, J. Zhu, W. E. Paul, W. J. Leonard, and S. M. Kaech. 2008. Formation of IL-7Ralphahigh and IL-7Ralphalow CD8 T cells during infection is regulated by the opposing functions of GABPalpha and Gfi-1. J. Immunol. 180:5309-5319.
57. Kerdiles, Y. M., D. R. Beisner, R. Tinoco, A. S. Dejean, D. H. Castrillon, R. A. De Pinho, and S. M. Hedrick. 2009. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat. Immunol. 10:176-184.
58. Feng, X., H. Wang, H. Takata, T. J. Day, J. Willen, and H. Hu. 2011. Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells. Nat. Immunol. 12:544-550.
59. Yang, C. Y., J. A. Best, J. Knell, E. Yang, A. D. Sheridan, A. K. Jesionek, H. S. Li, R. R. Rivera, K. C. Lind, L. M. D'Cruz, et al. 2011. The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat. Immunol. 12:1221-1229.
60. Mehta, D. S., R. A. Christmas, H. Waldmann, and M. Rosenzweig. 2010. Partial and transient modulation of the CD3-T-cell receptor complex, elicited by lowdose regimens of monoclonal anti-CD3, is sufficient to induce disease remission in non-obese diabetic mice. Immunology 130:103-113.
61. Esplugues, E., S. Huber, N. Gagliani, A. E. Hauser, T. Town, Y. Y. Wan, W. O'Connor, Jr., A. Rongvaux, N. Van Rooijen, A. M. Haberman, et al. 2011. Control of TH17 cells occurs in the small intestine. Nature 475:514-518.
62. Mackall, C. L., T. J. Fry, and R. E. Gress. 2011. Harnessing the biology of IL-7 for therapeutic application. Nat. Rev. Immunol. 11:330-342.
63. Liu, X., S. Leung, C. Wang, Z. Tan, J. Wang, T. B. Guo, L. Fang, Y. Zhao, B. Wan, X. Qin, et al. 2010. Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease. Nat. Med. 16:191-197.
64. Lee, L. F., K. Logronio, G. H. Tu, W. Zhai, I. Ni, L. Mei, J. Dilley, J. Yu, A. Rajpal, C. Brown, et al. 2012. Anti-IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function. Proc. Natl. Acad. Sci. USA 109:12674-12679.
65. Penaranda, C., W. Kuswanto, J. Hofmann, R. Kenefeck, P. Narendran, L. S. Walker, J. A. Bluestone, A. K. Abbas, and H. Dooms. 2012. IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells. Proc. Natl. Acad. Sci. USA 109:12668-12673.