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References

  • Akbar, A. N., Taams, L. S., Salmon, M., Vukmanovic-Stejic, M. (2003) The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology 109:319–325.

    Article  PubMed  CAS  Google Scholar 

  • Alyanakian, M. A., You, S., Damotte, D., et al. (2003) Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases. Proc. Natl. Acad. Sci. U S A 100:15806–15811.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, M. S., Bluestone, J. A. (2005) The NOD mouse: a model of immune dysregulation. Annu. Rev. Immunol. 23:447–485.

    Article  PubMed  CAS  Google Scholar 

  • Bensinger, S. J., Walsh, P. T., Zhang, J., et al. (2004) Distinct IL-2 receptor signaling pattern in CD4 + CD25+ regulatory T cells. J. Immunol. 172:5287–5296.

    PubMed  CAS  Google Scholar 

  • Bernard, C. C., de Rosbo, N. K. (1991) Immunopathological recognition of autoantigens in multiple sclerosis. Acta Neurol. 13:171–178.

    CAS  Google Scholar 

  • Bettelli, E., Dastrange, M., Oukka, M. (2005) Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl. Acad. Sci. U S A 102:5138–5143.

    Article  PubMed  CAS  Google Scholar 

  • Birebent, B., Lorho, R., Lechartier, H., et al. (2004) Suppressive properties of human CD4 + CD25+ regulatory T cells are dependent on CTLA-4 expression. Eur. J. Immunol. 34:3485–3496.

    Article  PubMed  CAS  Google Scholar 

  • Caton, A. J., Cozzo, C., Larkin, J., 3rd, et al. (2004) CD4(+) CD25(+) regulatory T cell selection. Ann. N. Y. Acad. Sci. 1029:101–114.

    Article  PubMed  CAS  Google Scholar 

  • Cederbom, L., Hall, H., Ivars, F. (2000) CD4 + CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur. J. Immunol. 30:1538–1543.

    Article  PubMed  CAS  Google Scholar 

  • Cozzo, C., Larkin, J., 3rd, Caton, A. J. (2003) Cutting edge: self-peptides drive the peripheral expansion of CD4 + CD25+ regulatory T cells. J. Immunol. 171:5678–5682.

    PubMed  CAS  Google Scholar 

  • De la Rosa, M., Rutz, S., Dorninger, H., Scheffold, A. (2004) Interleukin-2 is essential for CD4 + CD25+ regulatory T cell function. Eur. J. Immunol. 34:2480–2488.

    Article  PubMed  Google Scholar 

  • De Rosbo, N. K., Hoffman, M., Mendel, I., et al. (1997) Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions. Eur. J. Immunol. 27:3059–3069.

    Article  Google Scholar 

  • Ebers, G. C., Sadovnick, A. D., Risch, N. J. (1995) A genetic basis for familial aggregation in multiple sclerosis. Nature 377:150–151.

    Article  PubMed  CAS  Google Scholar 

  • Ermann, J., Hoffmann, P., Edinger, M., et al. (2005) Only the CD62L+ subpopulation of CD4 + CD25+ regulatory T cells protects from lethal acute GVHD. Blood 105:2220–2226.

    Article  PubMed  CAS  Google Scholar 

  • Fahlen, L., Read, S., Gorelik, L., et al. (2005) T cells that cannot respond to TGF-beta escape control by CD4(+) CD25(+) regulatory T cells. J. Exp. Med. 201:737–746.

    Article  PubMed  CAS  Google Scholar 

  • Fantini, M. C., Becker, C., Monteleone, G., et al. (2004) Cutting edge: TGF-beta induces a regulatory phenotype in CD4 + CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172:5149–5153.

    PubMed  CAS  Google Scholar 

  • Fisson, S., Darrasse-Jeze, G., Litvinova, E., et al. (2003) Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state. J. Exp. Med. 198:737–746.

    Article  PubMed  CAS  Google Scholar 

  • Fontenot, J. D., Gavin, M. A., Rudensky, A. Y. (2003) Foxp3 programs the development and function of CD4 + CD25+ regulatory T cells. Nat. Immunol. 4:330–336.

    Article  PubMed  CAS  Google Scholar 

  • Fujinami, R. S., Oldstone, M. B. (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:1043–1045.

    Article  PubMed  CAS  Google Scholar 

  • Furtado, G. C., Olivares-Villagomez, D., Curotto de Lafaille, M. A., et al. (2001) Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol. Rev. 182:122–134.

    Article  PubMed  CAS  Google Scholar 

  • Gallo, P., Cupic, D., Bracco, F., et al. (1989) Experimental allergic encephalomyelitis in the monkey: humoral immunity and blood-brain barrier function. Ital. J. Neurol. Sci. 10:561–565.

    PubMed  CAS  Google Scholar 

  • Ghiringhelli, F., Menard, C., Terme, M., et al. (2005) CD4 + CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J. Exp. Med. 202:1075–1085.

    Article  PubMed  CAS  Google Scholar 

  • Gondek, D. C., Lu, L. F., Quezada, S. A., et al. (2005) Cutting edge: contact-mediated suppression by CD4 + CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 174:1783–1786.

    PubMed  CAS  Google Scholar 

  • Gonzalez, A., Andre-Schmutz, I., Carnaud, C., et al. (2001) Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes. Nat. Immunol. 2:1117–1125.

    Article  PubMed  CAS  Google Scholar 

  • Green, E. A., Gorelik, L., McGregor, C. M., et al. (2003). CD4 + CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc. Natl. Acad. Sci. U S A 100:10878–10883.

    Article  PubMed  CAS  Google Scholar 

  • Hall, B. M., Pearce, N. W., Gurley, K. E., Dorsch, S. E. (1990). Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action. J. Exp. Med. 171:141–157.

    Article  PubMed  CAS  Google Scholar 

  • Janssens, W., Carlier, V., Wu, B., et al. (2003). CD4 + CD25+ T cells lyse antigen-presenting B cells by Fas-Fas ligand interaction in an epitope-specific manner. J. Immunol. 171:4604–4612.

    PubMed  CAS  Google Scholar 

  • Jordan, M. S., Boesteanu, A., Reed, A. J., et al. (2001). Thymic selection of CD4 + CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2:301–306.

    Article  PubMed  CAS  Google Scholar 

  • Kawahata, K., Misaki, Y., Yamauchi, M., et al. (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.

    PubMed  CAS  Google Scholar 

  • Kent, S. C., Chen, Y., Bregoli, L., et al. (2005) Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature 435:224–228.

    Article  PubMed  CAS  Google Scholar 

  • Khattri, R., Cox, T., Yasayko, S. A., Ramsdell, F. (2003) An essential role for Scurfin in CD4 + CD25+ T regulatory cells. Nat. Immunol. 4:337–342.

    Article  PubMed  CAS  Google Scholar 

  • King, I. L., Segal, B. M. (2005) Cutting edge: IL-12 induces CD4 + CD25- T cell activation in the presence of T regulatory cells. J. Immunol. 175:641–645.

    PubMed  CAS  Google Scholar 

  • Kohm, A. P., Carpentier, P. A., Anger, H. A., Miller, S. D. (2002) Cutting edge: CD4(+) CD25(+) regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169:4712–4716.

    PubMed  CAS  Google Scholar 

  • Kohm, A. P., Carpentier, P. A., Miller, S. D. (2003) Regulation of experimental autoimmune encephalomyelitis (EAE) by CD4 + CD25+ regulatory T cells. Novartis Found. Symp. 252:45–52.

    Article  PubMed  CAS  Google Scholar 

  • Kohm, A. P., McMahon, J. S., Podojil, J. R., et al. (2006) Anti-CD25 mAb injection results in the functional inactivation, not depletion of CD4 + CD25+ Treg cells. J. Immunol. 176(6):3301–3305.

    PubMed  CAS  Google Scholar 

  • Kohm, A. P., Williams, J. S., Bickford, A. L., et al. (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.

    PubMed  CAS  Google Scholar 

  • Kohm, A. P., Williams, J. S., Miller, S. D. (2004) Cutting edge : ligation of the glucocorticoid-induced TNF receptor enhances autoreactive CD4+ T cell activation and experimental autoimmune encephalomyelitis. J. Immunol. 172:4686–4690.

    PubMed  CAS  Google Scholar 

  • Kojima, A., Prehn, R. T. (1981) Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 14:15–27.

    Article  PubMed  CAS  Google Scholar 

  • Kurtzke, J. F. (1993) Epidemiologic evidence for multiple sclerosis as an infection. Clin. Microbiol. Rev. 6:382–427.

    PubMed  CAS  Google Scholar 

  • Lan, R. Y., Ansari, A. A., Lian, Z. X., Gershwin, M. E. (2005) Regulatory T cells: development, function and role in autoimmunity. Autoimmun. Rev. 4:351–363.

    Article  PubMed  CAS  Google Scholar 

  • Lim, H. W., Hillsamer, P., Banham, A. H., Kim, C. H. (2005) Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J. Immunol. 175:4180–4183.

    PubMed  CAS  Google Scholar 

  • Liu, Z., Geboes, K., Hellings, P., et al. (2001) B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis. J. Immunol. 167:1830–1838.

    PubMed  CAS  Google Scholar 

  • Lohmann, T., Leslie, R. D., Londei, M. (1996) T cell clones to epitopes of glutamic acid decarboxylase 65 raised from normal subjects and patients with insulin-dependent diabetes. J. Autoimmun. 9:385–389.

    Article  PubMed  CAS  Google Scholar 

  • Malek, T. R., Yu, A., Vincek, V., et al. (2002) CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17:167–178.

    Article  PubMed  CAS  Google Scholar 

  • Maloy, K. J., Salaun, L., Cahill, R., et al. (2003) CD4 + CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197:111–119.

    Article  PubMed  CAS  Google Scholar 

  • Marie, J. C., Letterio, J. J., Gavin, M., Rudensky, A. Y. (2005) TGF-beta1 maintains suppressor function and Foxp3 expression in CD4 + CD25+ regulatory T cells. J. Exp. Med. 201:1061–1067.

    Article  PubMed  CAS  Google Scholar 

  • McGeachy, M. J., Stephens, L. A., Anderton, S. M. (2005) Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4 + CD25+ regulatory cells within the central nervous system. J. Immunol. 175:3025–3032.

    PubMed  CAS  Google Scholar 

  • McHugh, R. S., Shevach, E. M. (2002) Cutting edge: depletion of CD4 + CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. J. Immunol. 168:5979–5983.

    PubMed  CAS  Google Scholar 

  • McHugh, R. S., Whitters, M. J., Piccirillo, C. A., et al. (2002) CD4(+) CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16:311–323.

    Article  PubMed  CAS  Google Scholar 

  • McRae, B. L., Vanderlugt, C. L., Dal Canto, M. C., Miller, S. D. (1995) Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J. Exp. Med. 182:75–85.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, M. E., van Bilsen, J. H., Bakker, A. M., et al. (2005) Expression of FOXP3 mRNA is not confined to CD4 + CD25+ T regulatory cells in humans. Hum. Immunol. 66:13–20.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, K., Kitani, A., Fuss, I., et al. (2004) TGF-beta 1 plays an important role in the mechanism of CD4 + CD25+ regulatory T cell activity in both humans and mice. J. Immunol. 172:834–842.

    PubMed  CAS  Google Scholar 

  • Nakamura, K., Kitani, A., Strober, W. (2001) Cell contact-dependent immunosuppression by CD4(+) CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J. Exp. Med. 194:629–644.

    Article  PubMed  CAS  Google Scholar 

  • Nakayama, M., Abiru, N., Moriyama, H., et al. (2005) Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 435:220–223.

    Article  PubMed  CAS  Google Scholar 

  • 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 94:6216–6221.

    Article  PubMed  CAS  Google Scholar 

  • Olson, J. K., Croxford, J. L., Miller, S. D. (2001) Virus-induced autoimmunity: potential role of viruses in initiation, perpetuation, and progression of T cell-mediated autoimmune diseases Viral Immunol. 14:227–250.

    Article  PubMed  CAS  Google Scholar 

  • Ota, K., Matsui, M., Milford, E. L., et al. (1990) T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187.

    Article  PubMed  CAS  Google Scholar 

  • Pacholczyk, R., Kraj, P., Ignatowicz, L. (2002) Peptide specificity of thymic selection of CD4 + CD25+ T cells. J. Immunol. 168:613–620.

    PubMed  CAS  Google Scholar 

  • Papiernik, M., de Moraes, M. L., Pontoux, C., et al. (1998) Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol. 10:371–378.

    Article  PubMed  CAS  Google Scholar 

  • Peng, Y., Laouar, Y., Li, M. O., et al. (2004) TGF-beta regulates in vivo expansion of Foxp3-expressing CD4 + CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. U S A 101:4572–4577.

    Article  PubMed  CAS  Google Scholar 

  • Piccirillo, C. A., Letterio, J. J., Thornton, A. M., et al. (2002) CD4(+) CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J. Exp. Med. 196:237–246.

    Article  PubMed  CAS  Google Scholar 

  • Piccirillo, C. A., Shevach, E. M. (2001) Cutting edge: control of CD8+ T cell activation by CD4 + CD25+ immunoregulatory cells. J. Immunol. 167:1137–1140.

    PubMed  CAS  Google Scholar 

  • Powrie, F., Carlino, J., Leach, M. W., et al. (1996) A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J. Exp. Med. 183:2669–2674.

    Article  PubMed  CAS  Google Scholar 

  • Reddy, J., Illes, Z., Zhang, X., et al. (2004) Myelin proteolipid protein-specific CD4 + CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. U S A 101:15434–15439.

    Article  PubMed  CAS  Google Scholar 

  • Romagnoli, P., Hudrisier, D., van Meerwijk, J. P. (2002) Preferential recognition of self antigens despite normal thymic deletion of CD4(+) CD25(+) regulatory T cells. J. Immunol. 168:1644–1648.

    PubMed  CAS  Google Scholar 

  • Ronchetti, S., Zollo, O., Bruscoli, S., et al. (2004) GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations. Eur. J. Immunol. 34:613–622.

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi, S., Sakaguchi, N. (1989) Organ-specific autoimmune disease induced in mice by elimination of T cell subsets. V. Neonatal administration of cyclosporin A causes autoimmune disease. J. Immunol. 142:471–480.

    PubMed  CAS  Google Scholar 

  • Sakaguchi, S., Sakaguchi, N., Asano, M., et al. (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.

    PubMed  CAS  Google Scholar 

  • Salomon, B., Lenschow, D. J., Rhee, L., et al. (2000) B7/CD28 costimulation is essential for the homeostasis of the CD4 + CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12:431–440.

    Article  PubMed  CAS  Google Scholar 

  • Shimizu, J., Yamazaki, S., Takahashi, T., et al. (2002) Stimulation of CD25(+) CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3:135–142.

    Article  PubMed  CAS  Google Scholar 

  • Suri-Payer, E., Amar, A. Z., Thornton, A. M., Shevach, E. M. (1998) CD4 + CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J. Immunol. 160:1212–1218.

    PubMed  CAS  Google Scholar 

  • Takahashi, T., Tagami, T., Yamazaki, S., et al. (2000) Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192:303–310.

    Article  PubMed  CAS  Google Scholar 

  • Tang, Q., Adams, J. Y., Tooley, A. J., et al. (2006) Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat. Immunol. 7:83–92.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, P. A., Panoskaltsis-Mortari, A., Swedin, J. M., et al. (2004) L-Selectin(hi) but not the L-selectin(lo) CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection. Blood 104:3804–3812.

    Article  PubMed  CAS  Google Scholar 

  • Thornton, A. M., Shevach, E. M. (1998) CD4 + CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188:287–296.

    Article  PubMed  CAS  Google Scholar 

  • Tone, M., Tone, Y., Adams, E., et al. (2003). Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells. Proc. Natl. Acad. Sci. U S A 100:15059–15064.

    Article  PubMed  CAS  Google Scholar 

  • Vanderlugt, C. L., Miller, S. D. (2002). Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat. Rev. Immunol. 2:85–95.

    Article  PubMed  CAS  Google Scholar 

  • Viglietta, V., Baecher-Allan, C., Weiner, H. L., Hafler, D. A. (2004). Loss of functional suppression by CD4 + CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199:971–979.

    Article  PubMed  CAS  Google Scholar 

  • Waksman, B. H. (1995) Multiple sclerosis: More genes versus environment. Nature 377: 105–106.

    Article  PubMed  CAS  Google Scholar 

  • Wekerle, H. (1991) Immunopathogenesis of multiple sclerosis. Acta Neurol. 13:197–204.

    CAS  Google Scholar 

  • Wong, F. S., Janeway, C. A. (1999) Insulin-dependent diabetes mellitus and its animal models. Curr. Opin. Immunol. 11:643–647.

    Article  PubMed  CAS  Google Scholar 

  • Wucherpfennig, K. W., Strominger, J. L. (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695–705.

    Article  PubMed  CAS  Google Scholar 

  • Zelenay, S., Lopes-Carvalho, T., Caramalho, I., 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. U S A 102:4091–4096.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, S. G., Gray, J. D., Ohtsuka, K., et al. (2002) Generation ex vivo of TGF-beta-producing regulatory T cells from CD4 + CD25-precursors. J. Immunol. 169:4183–4189.

    PubMed  CAS  Google Scholar 

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Kohm, A.P., Miller, S.D. (2007). CD4+CD25+ Regulatory T Cells in Autoimmune Disease. In: Zhang, J. (eds) Immune Regulation and Immunotherapy in Autoimmune Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-36003-4_9

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