Surge in regulatory cells does not prevent onset of hyperglycemia in NOD mice

References

• Gregori, S., N. Giarratana, S. Smiroldo, and L. Adorini. 2003. Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J. Immunol. 171: 4040–4047
   PubMed Web of Science ®Google Scholar
• You, S., M. Belghith, S. Cobbold, et al. 2005. Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells. Diabetes. 54: 1415–1422
   PubMed Web of Science ®Google Scholar
• Mellanby, R. J., D. Thomas, J. M. Phillips, and A. Cooke. 2007. Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+CD25+Foxp3+ regulatory T cells. Immunology. 121: 15–28
   PubMed Web of Science ®Google Scholar
• Serreze, D. V., E. A. Johnson, H. D. Chapman, et al. 2001. Autoreactive diabetogenic T-cells in NOD mice can efficiently expand from a greatly reduced precursor pool. Diabetes. 50: 1992–2000
   PubMed Web of Science ®Google Scholar
• Schneider, A., M. Rieck, S. Sanda, et al. 2008. The effector T cells of diabetic subjects are resistant to regulation via CD4+FOXP3+ regulatory T cells. J. Immunol. 181: 7350–7355
   PubMed Web of Science ®Google Scholar
• Lourenço, E. V., and A. La Cava. 2011. Natural regulatory T cells in autoimmunity. Autoimmunity. 44: 33–42
   PubMed Web of Science ®Google Scholar
• Yarkoni, S., T. B. Prigozhina, S. Slavin, and N. Askenasy. 2012. IL-2-targeted therapy ameliorates the severity of graft-versus-host disease: ex vivo selective depletion of host-reactive T cells and in vivo therapy. Biol. Blood Marrow Transplant. 18: 523–535
   PubMedGoogle Scholar
• Wu, A. J., H. Hua, S. H. Munson, and H. O. McDevitt. 2002. Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc. Natl. Acad. Sci. USA. 99: 12287–12292
   PubMed Web of Science ®Google Scholar
• Pop, S. M., C. P. Wong, D. A. Culton, et al. 2005. Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes. J. Exp. Med. 201: 1333–1346
   PubMed Web of Science ®Google Scholar
• Alard, P., J. N. Manirarora, S. A. Parnell, et al. 2006. Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice. Diabetes. 55: 2098–2105
   PubMed Web of Science ®Google Scholar
• Youngm, E. F., P. R. Hess, L. W. Arnold, et al. 2009. Islet lymphocyte subsets in male and female NOD mice are qualitatively similar but quantitatively distinct. Autoimmunity. 42: 678–691
   PubMedGoogle Scholar
• Tucker, C. F., D. L. Nebane-Ambe, and A. Chhabra. 2011. Decreased frequencies of CD4+CD25+Foxp3+ cells and the potent CD103+ subset in peripheral lymph nodes correlate with autoimmune disease predisposition in some strains of mice. Autoimmunity. 44: 453–464
   PubMed Web of Science ®Google Scholar
• Kukreja, A., G. Cost, J. Marker, et al. 2002. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 109: 131–140
   PubMed Web of Science ®Google Scholar
• Lindley, S., C. M. Dayan, A. Bishop, et al. 2005. Defective suppressor function in CD4+CD25+ T-cells from patients with type 1 diabetes. Diabetes. 54: 92–99
   PubMed Web of Science ®Google Scholar
• Putnam, A. L., F. Vendrame, F. Dotta, and P. A. Gottlieb. 2005. CD4+CD25high regulatory T cells in human autoimmune diabetes. J. Autoimmun. 24: 55–62
   PubMed Web of Science ®Google Scholar
• Brusko, T., C. Wasserfall, K. McGrail, et al. 2007. No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes. 56: 604–612
   PubMed Web of Science ®Google Scholar
• Tang, Q., J. Y. Adams, C. Penaranda, et al. 2008. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity. 28: 687–697
   PubMed Web of Science ®Google Scholar
• Tritt, M., E. Sgouroudis, E. d'Hennezel, et al. 2008. Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes. Diabetes. 57: 113–123
   PubMed Web of Science ®Google Scholar
• Berzins, S. P., E. S. Venanzi, C. Benoist, and D. Mathis. 2003. T-cell compartments of prediabetic NOD mice. Diabetes. 52: 327–334
   PubMed Web of Science ®Google Scholar
• Nakahara, M., Y. Nagayama, T. Ichikawa, et al. 2011. The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages. Autoimmunity. 44: 504–510
   PubMed Web of Science ®Google Scholar
• Gregg, R. K., R. Jain, S. J. Schoenleber, et al. 2004. A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes. J. Immunol. 173: 7308–7316
   PubMed Web of Science ®Google Scholar
• Kawamotom, K., A. Pahuja, A. Nettles, et al. 2012. Downregulation of TGF-βRII in T effector cells leads to increased resistance to TGF-β-mediated suppression of autoimmune responses in type I diabetes. Autoimmunity. 45: 310–319
   PubMedGoogle Scholar
• Decallonne, B., E. van Etten, A. Giulietti, et al. 2003. Defect in activation induced cell death in non-obese diabetic (NOD) T lymphocytes. J. Autoimmun. 20: 219–226
   PubMedGoogle Scholar
• Arreaza, G., K. Salojin, W. Yang, et al. 2003. Deficient activation and resistance to activation-induced apoptosis of CD8+ T cells is associated with defective peripheral tolerance in nonobese diabetic mice. Clin. Immunol. 107: 103–115
   PubMedGoogle Scholar
• D'Alise, A. M., V. Auyeung, M. Feuerer, et al. 2008. The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc. Natl. Acad. Sci. USA. 105: 19857–19862
   PubMedGoogle Scholar
• Kaminitz, A., E. S. Yolcu, E. M. Askenasy, et al. 2011. Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice. PLoS One. 6: e21630
   Google Scholar
• Yarkoni, S., A. Kaminitz, Y. Sagiv, and N. Askenasy. 2010. Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice. Diabetologia. 53: 356–368
   PubMed Web of Science ®Google Scholar
• Kaminitz, A., K. Mizrahi, I. Yaniv, et al. 2009. Low levels of allogeneic but not syngeneic hematopoietic chimerism reverse autoimmune insulitis in prediabetic NOD mice. J. Autoimmun. 33: 83–91
   PubMed Web of Science ®Google Scholar
• Kaminitz, A., E. S. Yolcu, K. Mizrahi, et al. 2013. Killer Treg cells ameliorate inflammatory insulitis in non-obese diabetic mice through local and systemic immunomodulation. Int. Immunol. 25: 485--494
   Google Scholar
• Kaminitz, A., E. S. Yolcu, J. Stein, et al. 2011. Killer Treg restore immune homeostasis and suppress autoimmune diabetes in prediabetic NOD mice. J. Autoimmun. 37: 39–47
   PubMed Web of Science ®Google Scholar
• Stephens, L. A., and D. Mason. 2000. CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25- subpopulations. J. Immunol. 165: 3105–3110
   PubMedGoogle Scholar
• Gavin, M. A., S. R. Clarke, E. Negrou, et al. 2002. Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo. Nat. Immunol. 3: 33–41
   PubMed Web of Science ®Google Scholar
• Pedersen, A. E. and J. P. Lauritsen. 2009. CD25 shedding by human natural occurring CD4+CD25+ regulatory T cells does not inhibit the action of IL-2. Scand. J. Immunol. 70: 40–43
   PubMed Web of Science ®Google Scholar
• Kaminitz, A., E. M. Askenasy, I. Yaniv, et al. 2010. Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice. PLoS One. 5: e15684
   Google Scholar
• Askenasy, E. M., and N. Askenasy. 2012. Is autoimmune diabetes caused by aberrant immune activity or defective suppression of physiological self-reactivity? Autoimmun. Rev. 12: 633–637
   PubMedGoogle Scholar
• Feuerer, M., W. Jiang, P. D. Holler, et al. 2007. Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes. Proc. Natl. Acad. Sci. USA. 104: 18181–18186
   PubMed Web of Science ®Google Scholar
• Tellier, J., A. Andrianjaka, R. Vincente, et al. 2013. Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility. Eur. J. Immunol. 43: 1356–1362
   PubMedGoogle Scholar
• Zelenay, S., T. Lopes-Carvalho, I. Caramalho, et al. 2005. Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc. Natl. Acad. Sci. USA. 102: 4091–4096
   PubMed Web of Science ®Google Scholar
• Komatsu, N., M. E. Mariotti-Ferrandiz, Y. Wang, et al. 2009. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. USA. 106: 1903–1908
   PubMed Web of Science ®Google Scholar
• Graham, K. L., B. Krishnamurthy, S. Fynch, et al. 2012. Intra-islet proliferation of cytotoxic T lymphocytes contributes to insulitis progression. Eur. J. Immunol. 42: 1717–1722
   PubMedGoogle Scholar
• Chen, W., W. Jin, N. Hardegen, et al. 2003. 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
   PubMed Web of Science ®Google Scholar
• Curotto de Lafaille, M. A., A. C. Lino, N. Kutchukhidze, and J. J. Lafaille. 2004. CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J. Immunol. 173: 7259–7268
   PubMed Web of Science ®Google Scholar
• Liang, S., P. Alard, Y. Zhao, et al. 2005. Conversion of CD4+ CD25- cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus. J. Exp. Med. 201: 127–137
   PubMed Web of Science ®Google Scholar
• Zhou, X., N. Kong, H. Zou, et al. 2011. Therapeutic potential of TGF-β-induced CD4+ Foxp3+ regulatory T cells in autoimmune diseases. Autoimmunity. 44: 43–50
   PubMed Web of Science ®Google Scholar
• Thomas, H. E., K. L. Graham, J. Chee, et al. 2013. Proinflammatory cytokines contribute to development and function of regulatory T cells in type 1 diabetes. Ann. N. Y. Acad. Sci. 1283: 81–86
   PubMedGoogle Scholar
• Yarkoni, S., A. Kaminitz, Y. Sagiv, et al. 2008. Involvement of IL-2 in homeostasis of regulatory T cells: the IL-2 cycle. Bioessays. 30: 875–888
   PubMed Web of Science ®Google Scholar
• Sgouroudis, E., M. Kornete, and C. A. Piccirillo. 2011. IL-2 production by dendritic cells promotes Foxp3+ regulatory T-cell expansion in autoimmune-resistant NOD congenic mice. Autoimmunity. 44: 406–414
   PubMed Web of Science ®Google Scholar
• Grinberg-Bleyer, Y., A. Baeyens, S. You, et al. 2010. IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J. Exp. Med. 207: 1871–1878
   PubMed Web of Science ®Google Scholar
• Tonkin, D. R., J. He, G. Barbour, and K. Haskins. 2008. Regulatory T cells prevent transfer of type 1 diabetes in NOD mice only when their antigen is present in vivo. J. Immunol. 181: 4516–4522
   PubMedGoogle Scholar
• Yolcu, E. S., S. Ash, A. Kaminitz, et al. 2008. Apoptosis as a mechanism of T-regulatory cell homeostasis and suppression. Immunol. Cell. Biol. 86: 650–658
   PubMed Web of Science ®Google Scholar
• Pandiyan, P., L. Zheng, S. Ishihara, et al. 2007. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol. 8: 1353–3162
   PubMed Web of Science ®Google Scholar
• Kaminitz, A., J. Stein, I. Yaniv, and N. Askenasy. 2007. The vicious cycle of apoptotic beta-cell death in type 1 diabetes. Immunol. Cell. Biol. 85: 582–589
   PubMedGoogle Scholar
• Pandiyan, P., and M. J. Lenardo. 2008. The control of CD4+CD25+Foxp3+ regulatory T cell survival. Biol. Direct. 3: 6 . doi:10.1186/1745-6150-3-6
   PubMed Web of Science ®Google Scholar
• Grinberg-Bleyer, Y., D. Saadoun, A. Baeyens, et al. 2010. Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs. J. Clin. Invest. 120: 4558–4568
   PubMedGoogle Scholar
• Billiard, F., E. Litvinova, D. Saadoun, et al. 2006. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J. Immunol. 177: 2167–2174
   PubMed Web of Science ®Google Scholar
• Sojka, D. K., C. A. Lazarski, Y. H. Huang, et al. 2009. Regulation of immunity at tissue sites of inflammation. Immunol. Res. 45: 239–250
   PubMedGoogle Scholar
• Askenasy, N., A. Kaminitz, and S. Yarkoni. 2008. Mechanisms of T regulatory cell function. Autoimmun. Rev. 7: 370–375
   PubMed Web of Science ®Google Scholar
• Vignali, D. A. A. 2012. Mechanisms of Treg suppression: still a long way to go. Front. Immunol. 3: 191 . doi: 10.3389/fimmu.2012.00191
   PubMedGoogle Scholar
• Kornete, M., H. Beauchemin, C. Polychronakos, and C. A. Piccirillo. 2013. Pancreatic islet cell phenotype and endocrine function throughout diabetes development in non-obese diabetic mice. Autoimmunity. 46: 259–268
   PubMed Web of Science ®Google Scholar
• Delovitch, T. L., and B. Singh. 1997. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 7: 727–738
   PubMed Web of Science ®Google Scholar
• Anderson, M. S., and J. A. Bluestone. 2005. The NOD mouse: a model of immune dysregulation. Annu. Rev. Immunol. 23: 447–485
   PubMed Web of Science ®Google Scholar
• Sgouroudis, E., and C. A. Piccirillo. 2009. Control of type 1 diabetes by CD4+Foxp3+ regulatory T cells: lessons from mouse models and implications for human disease. Diabetes Metab. Res. Rev. 25: 208–218
   PubMedGoogle Scholar
• Driver, J. P., D. V. Serreze, and Y. G. Chen. 2011. Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human disease. Semin. Immunopathol. 33: 67–87
   PubMed Web of Science ®Google Scholar