Low frequency of GITR+ T cells in ex vivo and in vitro expanded Treg cells from type 1 diabetic patients

International Immunology

Volumn 25, Issue 10, 2013, Pages 563-574

  Xufré, Cristina ^a   Costa, Manuela ^a   Roura Mir, Carme ^a   Codina Busqueta, Eva ^a   Usero, Lorena ^a   Pizarro, Eduarda ^b   Obiols, Gabriel ^c   Jaraquemada, Dolores ^a   Martí, Mercè ^a  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b HOSPITAL DE MATARÓ   (Spain)

^c HOSPITAL CLÍNIC   (Spain)

Author keywords

Autoimmunity; Cell surface markers; Treg cell expansion

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; INTERLEUKIN 7 RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ADULT; APOPTOSIS; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CELL SURVIVAL; CONTROLLED STUDY; EX VIVO STUDY; FEMALE; FLOW CYTOMETRY; FLUORESCENCE; HUMAN; IN VITRO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; LYMPHOCYTE SUBPOPULATION; MAJOR CLINICAL STUDY; MALE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

AUTOIMMUNITY; CELL SURFACE MARKERS; TREG-CELL EXPANSION;

ADULT; ANTIGENS, CD4; CELL SEPARATION; CELL SURVIVAL; DIABETES MELLITUS, TYPE 1; FEMALE; FLOW CYTOMETRY; GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN; HUMANS; IMMUNOPHENOTYPING; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; MALE; MIDDLE AGED; T-LYMPHOCYTES, REGULATORY; YOUNG ADULT;

EID: 84884723400     PISSN: 09538178     EISSN: 14602377     Source Type: Journal    
DOI: 10.1093/intimm/dxt020     Document Type: Article

References (49)

1. Nishizuka, Y. and Sakakura, T. 1969. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166:753.
2. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and Toda, M. 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.
3. Larkin, J., III, Rankin, A. L., Picca, C. C. et al. 2008. CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen. J. Immunol. 180:2149.
4. Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A. et al. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27:68.
5. Bennett, C. L. and Ochs, H. D. 2001. IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr. Opin. Pediatr. 13:533.
6. Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330.
7. Seddiki, N., Santner-Nanan, B., Martinson, J. et al. 2006. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203:1693.
8. Levings, M. K., Sangregorio, R., Sartirana, C. et al. 2002. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells. J. Exp. Med. 196:1335.
9. Wing, K., Ekmark, A., Karlsson, H., Rudin, A. and Suri-Payer, E. 2002. Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood. Immunology 106:190.
10. Walker, M. R., Kasprowicz, D. J., Gersuk, V. H. et al. 2003. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 112:1437.
11. Floess, S., Freyer, J., Siewert, C. et al. 2007. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5:e38.
12. Kriegel, M. A., Lohmann, T., Gabler, C., Blank, N., Kalden, J. R. and Lorenz, H. M. 2004. Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J. Exp. Med. 199:1285.
13. Viglietta, V., Baecher-Allan, C., Weiner, H. L. and Hafler, D. A. 2004. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199:971.
14. Marazuela, M., García-López, M. A., Figueroa-Vega, N. et al. 2006. Regulatory T cells in human autoimmune thyroid disease. J. Clin. Endocrinol. Metab. 91:3639.
15. Kukreja, A., Cost, G., Marker, J. et al. 2002. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 109:131.
16. Brusko, T. M., Wasserfall, C. H., Clare-Salzler, M. J., Schatz, D. A. and Atkinson, M. A. 2005. Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 54:1407.
17. Lindley, S., Dayan, C. M., Bishop, A., Roep, B. O., Peakman, M. and Tree, T. I. 2005. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 54:92.
18. high regulatory T cells in human autoimmune diabetes. J. Autoimmun. 24:55.
19. Schneider, A., Rieck, M., Sanda, S., Pihoker, C., Greenbaum, C. and Buckner, J. H. 2008. The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J. Immunol. 181:7350.
20. reg can be generated from CD4+CD25- T cells of healthy and type 1 diabetic subjects. Eur. J. Immunol. 39:612.
21. Long, S. A., Cerosaletti, K., Bollyky, P. L. et al. 2010. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes 59:407.
22. Lowe, C. E., Cooper, J. D., Brusko, T. et al. 2007. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat. Genet. 39:1074.
23. Livak, K. J. and Schmittgen, T. D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402.
24. Lossos, I. S., Czerwinski, D. K., Wechser, M. A. and Levy, R. 2003. Optimization of quantitative real-time RT-PCR parameters for the study of lymphoid malignancies. Leukemia 17:789.
25. Riddell, S. R. and Greenberg, P. D. 1990. The use of anti-CD3 and anti-CD28 monoclonal antibodies to clone and expand human antigen-specific T cells. J. Immunol. Methods 128:189.
26. Fritzsching, B., Oberle, N., Eberhardt, N. et al. 2005. In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death. J. Immunol. 175:32.
27. Michalek, J., Vrabelova, Z., Hrotekova, Z. et al. 2006. Immune regulatory T cells in siblings of children suffering from type 1 diabetes mellitus. Scand. J. Immunol. 64:531.
28. Tree, T. I., Roep, B. O. and Peakman, M. 2006. A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the Immunology of Diabetes Society T Cell Workshop. Ann. N. Y. Acad. Sci. 1079:9.
29. Jin, Y., Chen, X., Podolsky, R. et al. 2009. APC dysfunction is correlated with defective suppression of T cell proliferation in human type 1 diabetes. Clin. Immunol. 130:272.
30. McClymont, S. A., Putnam, A. L., Lee, M. R. et al. 2011. Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J. Immunol. 186:3918.
31. Ferraro, A., Socci, C., Stabilini, A. et al. 2011. Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 60:2903.
32. Nervi, S., Atlan-Gepner, C., Fossat, C. and Vialettes, B. 1999. Constitutive impaired TCR/CD3-mediated activation of T cells in IDDM patients co-exist with normal co-stimulation pathways. J. Autoimmun. 13:247.
33. Nocentini, G., Giunchi, L., Ronchetti, S. et al. 1997. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc. Natl. Acad. Sci. U. S. A. 94:6216.
34. Azuma, M. 2010. Role of the glucocorticoid-induced TNFRrelated protein (GITR)-GITR ligand pathway in innate and adaptive immunity. Crit. Rev. Immunol. 30:547.
35. Nocentini, G., Ronchetti, S., Petrillo, M. G. and Riccardi, C. 2012. Pharmacological modulation of GITRL/GITR system: therapeutic perspectives. Br. J. Pharmacol. 165:2089.
36. Luczynski, W., Wawrusiewicz-Kurylonek, N., Stasiak-Barmuta, A. et al. 2009. Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. Acta Biochim. Pol. 56:361.
37. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y. and Sakaguchi, S. 2002. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3:135.
38. Placke, T., Kopp, H. G. and Salih, H. R. 2010. Glucocorticoidinduced TNFR-related (GITR) protein and its ligand in antitumor immunity: functional role and therapeutic modulation. Clin. Dev. Immunol. 2010:239083.
39. Tuyaerts, S., Van Meirvenne, S., Bonehill, A. et al. 2007. Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells. J. Leukoc. Biol. 82:93.
40. Bianchini, R., Bistoni, O., Alunno, A. et al. 2011. CD4(+) CD25(low) GITR(+) cells: a novel human CD4(+) T-cell population with regulatory activity. Eur. J. Immunol. 41:2269.
41. Putnam, A. L., Brusko, T. M., Lee, M. R. et al. 2009. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 58:652-662.
42. van Olffen, R. W., Koning, N., van Gisbergen, K. P. et al. 2009. GITR triggering induces expansion of both effector and regulatory CD4+ T cells in vivo. J. Immunol. 182:7490.
43. Howie, D., Nolan, K. F., Daley, S. et al. 2009. MS4A4B is a GITRassociated membrane adapter, expressed by regulatory T cells, which modulates T cell activation. J. Immunol. 183:4197.
44. Carrier, Y., Whitters, M. J., Miyashiro, J. S. et al. 2012. Enhanced GITR/GITRL interactions augment IL-27 expression and induce IL-10-producing Tr-1 like cells. Eur. J. Immunol. 42:1393.
45. Ray, A., Basu, S., Williams, C. B., Salzman, N. H. and Dittel, B. N. 2012. A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand. J. Immunol. 188:3188.
46. Nocentini, G., Cuzzocrea, S., Genovese, T. et al. 2008. Glucocorticoid-induced tumor necrosis factor receptor-related (GITR)-Fc fusion protein inhibits GITR triggering and protects from the inflammatory response after spinal cord injury. Mol. Pharmacol. 73:1610.
47. Spinicelli, S., Nocentini, G., Ronchetti, S., Krausz, L. T., Bianchini, R. and Riccardi, C. 2002. GITR interacts with the proapoptotic protein Siva and induces apoptosis. Cell Death Differ. 9:1382.
48. Glisic-Milosavljevic, S., Waukau, J., Jailwala, P. et al. 2007. At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction. PLoS One. 2:e146.
49. Jailwala, P., Waukau, J., Glisic, S. et al. 2009. Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation. PLoS One. 4:e6527.