Skip to main content
SpringerLink
Log in

The Use of CD3-Specific Antibodies in Autoimmune Diabetes: A Step Toward the Induction of Immune Tolerance in the Clinic

  • Chapter
Therapeutic Antibodies

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 181))

CD3-specific monoclonal antibodies were the first rodent monoclonals introduced in clinical practice in the mid 1980s as approved immunosuppressants to prevent and treat organ allograft rejection. Since then compelling evidence has been accumulated to suggest that in addition to their immunosuppressive properties, CD3-specific antibodies can also afford inducing immune tolerance especially in the context of ongoing immune responses. Thus, they are highly effective at restoring self-tolerance in overt autoimmunity, a capacity first demonstrated in the experimental setting, which was recently transferred to the clinic with success.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abramowicz D, Schandene L et al. (1989) Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 47(4):606-608

    PubMed  Google Scholar 

  • Adler SH, Turka LA (2002) Immunotherapy as a means to induce transplantation tolerance. Curr Opin Immunol 14(5):660-665

    PubMed  Google Scholar 

  • Akashi T, Nagafuchi S et al. (1997) Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice. Int Immunol 9 (8):1159-1164

    PubMed  Google Scholar 

  • Alegre ML, Peterson LJ et al. (1994) A non-activating “humanized” anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. Transplantation 57(11):1537-1543

    PubMed  Google Scholar 

  • Asano M, Toda M et al. (1996) Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 184(2):387-396

    PubMed  Google Scholar 

  • Bach JF (1994) Insulin-dependent diabetes mellitus as an autoimmune disease. Endocrine Rev 15(4):516-542

    Google Scholar 

  • Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347(12):911-920

    PubMed  Google Scholar 

  • Bach JF, Chatenoud L (2001) Tolerance to islet autoantigens and type I diabetes. Annu Rev Immunol 19:131-161

    PubMed  Google Scholar 

  • Baekkeskov S, Aanstoot HJ et al. (1990) Identification of the 64K autoantigen in insulindependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347 (6289):151-156

    PubMed  Google Scholar 

  • Baxter AG, Horsfall AC et al. (1994) Mycobacteria precipitate an SLE-like syndrome in diabetesprone NOD mice. Immunology 83(2):227-231

    PubMed  Google Scholar 

  • Baxter AG, Mandel TE (1991) Hemolytic anemia in non-obese diabetic mice. Eur J Immunol 21(9):2051-2055

    PubMed  Google Scholar 

  • Belghith M, Bluestone JA et al. (2003) TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 9(9):1202-1208

    PubMed  Google Scholar 

  • Bendelac A, Carnaud C et al. (1987) Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J Exp Med 166 (4):823-832

    PubMed  Google Scholar 

  • Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3(3):253-257

    PubMed  Google Scholar 

  • Boitard C, Yasunami R et al. (1989) T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice. J Exp Med 169(5):1669-1680

    PubMed  Google Scholar 

  • Bolt S, Routledge E et al. (1993) The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol 23(2):403-411

    PubMed  Google Scholar 

  • Bottazzo GF, Florin-christensen A et al. (1974) Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 2(7892):1279-1283

    PubMed  Google Scholar 

  • Charlton B, Bacelj A et al. (1989) Cyclophosphamide-induced diabetes in NOD/WEHI mice. Evidence for suppression in spontaneous autoimmune diabetes mellitus. Diabetes 38(4):441-447

    PubMed  Google Scholar 

  • Chatenoud L (2003) CD3-specific antibody-induced active tolerance: from bench to bedside. Nat Rev Immunol 3(2):123-132

    PubMed  Google Scholar 

  • Chatenoud L, Bach JF (1984) Antigenic modulation: a major mechanism of antibody action. Immunol Today 5(1):20-25

    Google Scholar 

  • Chatenoud L, Baudrihaye MF et al. (1986) Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3. J Immunol 137(3):830-838

    PubMed  Google Scholar 

  • Chatenoud L, Baudrihaye MF et al. (1982) Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur J Immunol 12(11):979-982

    PubMed  Google Scholar 

  • Chatenoud L, Ferran C et al. (1990) In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. Transplantation 49(4):697-702

    PubMed  Google Scholar 

  • Chatenoud L, Ferran C et al. (1989) “Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma. N Engl J Med 320(21):1420-1421

    PubMed  Google Scholar 

  • Chatenoud L, Primo J et al. (1997) CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 158(6):2947-2954

    PubMed  Google Scholar 

  • Chatenoud L, Thervet E et al. (1994) Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 91(1):123-127

    PubMed  Google Scholar 

  • Christianson SW, Shultz LD et al. (1993) Adoptive transfer of diabetes into immunodeficient NODscid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes 42(1):44-55

    PubMed  Google Scholar 

  • Clevers H, Alarcon B et al. (1988) The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol 6(1):629-662

    PubMed  Google Scholar 

  • Cobbold SP, Adams E et al. (1996) Mechanisms of peripheral tolerance and suppression induced by monoclonal antibodies to CD4 and CD8. Immunol Rev 149:5-33

    PubMed  Google Scholar 

  • Cobbold SP, Qin S et al. (1992) Reprogramming the immune system for peripheral tolerance with CD4 and CD8 monoclonal antibodies. Immunol Rev 129:165-201

    PubMed  Google Scholar 

  • Cosimi AB (1987) Clinical development of Orthoclone OKT3. Transplant Proc 19(2 Suppl 1):7-16

    PubMed  Google Scholar 

  • Cosimi AB, Burton RC et al. (1981a) Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation 32(6):535-539

    Google Scholar 

  • Cosimi AB, Colvin RB et al. (1981b) Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts. N Engl J Med 305(6):308-314

    Google Scholar 

  • Crisa L, Mordes JP et al. (1992) Autoimmune diabetes mellitus in the BB rat. Diabetes Metab Rev 8(1):4-37

    PubMed  Google Scholar 

  • Daniel D, Gill RG et al. (1995) Epitope specificity, cytokine production profile and diabetogenic activity of insulin-specific T cell clones isolated from NOD mice. Eur J Immunol 25(4):1056-1062

    PubMed  Google Scholar 

  • Dardenne M, Lepault F et al. (1989) Acceleration of the onset of diabetes in NOD mice by thymectomy at weaning. Eur J Immunol 19(5):889-895

    PubMed  Google Scholar 

  • Davis MM, Chien YH (1999) T cell antigen receptors. In: Paul W (ed) Fundamental immunology. Raven, New York, pp 341-366

    Google Scholar 

  • Debure A, Chkoff N et al. (1988) One-month prophylactic use of OKT3 in cadaver kidney transplant recipients. Transplantation 45(3):546-553

    PubMed  Google Scholar 

  • Decochez K, Keymeulen B et al. (2000) Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry. Diabetes Care 23(8):1072-1078

    PubMed  Google Scholar 

  • Dotta F, Dionisi S et al. (1999) T-cell mediated autoimmunity to the insulinoma-associated protein 2 islet tyrosine phosphatase in type 1 diabetes mellitus. Eur J Endocrinol 141(3):272-278

    PubMed  Google Scholar 

  • Eason JD, Cosimi AB (1999) Biologic immunosuppressive agents. In: Ginns L, Cosimi A, Morris P (eds) Transplantation. Blackwell, Malden, USA, pp 196-224

    Google Scholar 

  • Elias D, Cohen IR (1994) Peptide therapy for diabetes in NOD mice. Lancet 343(8899):704-706

    PubMed  Google Scholar 

  • Elias D, Meilin A et al. (1997) Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta-cell antigens. Diabetes 46 (5):758-764

    PubMed  Google Scholar 

  • Elias D, Reshef T et al. (1991) Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. Proc Natl Acad Sci USA 88(8):3088-3091

    PubMed  Google Scholar 

  • Feutren G, Papoz L et al. (1986) Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet 2 (8499):119-124

    PubMed  Google Scholar 

  • French MB, Allison J et al. (1997) Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice. Diabetes 46(1):34-39

    PubMed  Google Scholar 

  • Friend PJ, Hale G et al. (1999) Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection. Transplantation 68:1632-1637

    PubMed  Google Scholar 

  • Fujino-kurihara H, Fujita H et al. (1985) Morphological aspects on pancreatic islets of non-obese diabetic (NOD) mice. Virchows Arch B Cell Pathol Incl Mol Pathol 49(2):107-120

    PubMed  Google Scholar 

  • Garchon HJ, Bedossa P et al. (1991) Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice. Nature 353(6341):260-262

    PubMed  Google Scholar 

  • Gomez-Reino JJ, Carmona L et al. (2003) Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter activesurveillance report. Arthritis Rheum 48(8):2122-2127

    PubMed  Google Scholar 

  • Harrison LC, Honeyman MC et al. (1997) A peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice. J Exp Med 185 (6):1013-1021

    PubMed  Google Scholar 

  • Hawkes CJ, Wasmeier C et al. (1996) Identification of the 37-kDa antigen in IDDM as a tyrosine phosphatase-like protein (phogrin) related to IA-2. Diabetes 45(9):1187-1192

    PubMed  Google Scholar 

  • Hayward AR, Shreiber M (1989) Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes. J Immunol 143(5):1555-1559

    PubMed  Google Scholar 

  • Herbelin A, Gombert JM et al. (1998) Mature mainstream TCR alpha beta(+)CD4(+) thymocytes expressing L-selectin mediate “active tolerance” in the nonobese diabetic mouse. J Immunol 161 (5):2620-2628

    PubMed  Google Scholar 

  • Herold KC, Gitelman SE et al. (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(6):1763-1769

    PubMed  Google Scholar 

  • Herold KC, Hagopian W et al. (2002) Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346(22):1692-1698

    PubMed  Google Scholar 

  • Hirsch R, Bluestone JA et al. (1990) Anti-CD3 F(ab′ )2 fragments are immunosuppressive in vivo without evoking either the strong humoral response or morbidity associated with whole mAb. Transplantation 49(6):1117-1123

    PubMed  Google Scholar 

  • Honeyman MC, Cram DS et al. (1993) Glutamic acid decarboxylase 67-reactive T cells: a marker of insulin-dependent diabetes. J Exp Med 177(2):535-540

    PubMed  Google Scholar 

  • Humphreys Beher MG, Brinkley L et al. (1993) Characterization of antinuclear autoantibodies present in the serum from nonobese diabetic (NOD) mice. Clin Immunol Immunopathol 68 (3):350-356

    PubMed  Google Scholar 

  • Katz JD, Wang B et al. (1993) Following a diabetogenic T cell from genesis through pathogenesis. Cell 74(6):1089-1100

    PubMed  Google Scholar 

  • Keane J, Gershon S et al. (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345(15):1098-1104

    PubMed  Google Scholar 

  • Keymeulen B, Vandemeulebroucke E et al. (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352(25):2598-2608

    PubMed  Google Scholar 

  • Kohm AP, Williams JS 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(8):4525-4534

    PubMed  Google Scholar 

  • Kung P, Goldstein G et al. (1979) Monoclonal antibodies defining distinctive human T cell surface antigens. Science 206(4416):347-349

    PubMed  Google Scholar 

  • Lampasona V, Bearzatto M et al. (1996) Autoantibodies in insulin-dependent diabetes recognize distinct cytoplasmic domains of the protein tyrosine phosphatase-like IA-2 autoantigen. J Immunol 157(6):2707-2711

    PubMed  Google Scholar 

  • Langer-Gould A, Atlas SW et al. (2005) Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353(4):375-381

    PubMed  Google Scholar 

  • Leo O, Foo M et al. (1987) Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci USA 84(5):1374-1378

    PubMed  Google Scholar 

  • Lepault F, Gagnerault MC (2000) Characterization of peripheral regulatory CD4(+) T cells that prevent diabetes onset in nonobese diabetic mice. J Immunol 164(1):240-247

    PubMed  Google Scholar 

  • Lieberman SM, Evans AM et al. (2003) Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc Natl Acad Sci USA 100 (14):8384-8388

    PubMed  Google Scholar 

  • Ludviksson BR, Ehrhardt RO et al. (1997) TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice. J Immunol 159(7):3622-3628

    PubMed  Google Scholar 

  • Mahiou J, Walter U et al. (2001) In vivo Blockade of the Fas-Fas Ligand Pathway Inhibits Cyclophosphamide-induced Diabetes in NOD Mice. J Autoimmun 16(4):431-440

    PubMed  Google Scholar 

  • Maki T, Ichikawa T et al. (1992) Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc Natl Acad Sci USA 89 (8):3434-3438

    PubMed  Google Scholar 

  • Makino S, Kunimoto K et al. (1980) Breeding of a non-obese, diabetic strain of mice. Exp Anim 29(1):1-13

    Google Scholar 

  • Many MC, Maniratunga S et al. (1996) The non-obese diabetic (NOD) mouse: An animal model for autoimmune thyroiditis. Exp Clin Endocrinol Diabetes 104:17-20

    PubMed  Google Scholar 

  • Many MC, Maniratunga S et al. (1995) Two-step development of Hashimoto-like thyroiditis in genetically autoimmune prone non-obese diabetic mice: effects of iodine-induced cell necrosis. J Endocrinol 147(2):311-320

    PubMed  Google Scholar 

  • Nakhooda AF, Like AA et al. (1977) The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26(2):100-112

    PubMed  Google Scholar 

  • Nicolls MR, Aversa GG et al. (1993) Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation 55(3):459-468

    PubMed  Google Scholar 

  • Nishizuka Y, Sakakura T (1969) Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166(906):753-755

    PubMed  Google Scholar 

  • Noorchashm H, Noorchashm N et al. (1997) B-cells are required for the initiation of insulitis and sialitis in nonobese diabetic mice. Diabetes 46(6):941-946

    PubMed  Google Scholar 

  • Ohsugi T, Kurosawa T (1994) Increased incidence of diabetes mellitus in specific pathogeneliminated offspring produced by embryo transfer in NOD mice with low incidence of the disease. Lab Anim Sci 44(4):386-388

    PubMed  Google Scholar 

  • Ortho Multicenter Transplant Study Group (1985) A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 313(6):337-342

    Google Scholar 

  • Panina-bordignon P, Lang R et al. (1995) Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med 181(5):1923-1927

    PubMed  Google Scholar 

  • Parlevliet KJ, Ten Berge IJ et al. (1994) In vivo effects of IgA and IgG2a anti-CD3 isotype switch variants. J Clin Invest 93(6): 2519-2525

    PubMed  Google Scholar 

  • Plain KM, Chen J et al. (1999) Induction of specific tolerance to allografts in rats by therapy with non-mitogenic, non-depleting anti-CD3 monoclonal antibody: association with TH2 cytokines not anergy. Transplantation 67(4):605-613

    PubMed  Google Scholar 

  • Quezada SA, Jarvinen LZ et al. (2004) CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307-328

    PubMed  Google Scholar 

  • Rohane PW, Shimada A et al. (1995) Islet-infiltrating lymphocytes from prediabetic NOD mice rapidly transfer diabetes to NOD-scid/scid mice. Diabetes 44(5):550-554

    PubMed  Google Scholar 

  • Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25 + CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345-352

    PubMed  Google Scholar 

  • Salomon B, Lenschow DJ 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

    PubMed  Google Scholar 

  • Sempe P, Bedossa P et al. (1991) Anti-alpha/beta T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice. Eur J Immunol 21 (5):1163-1169

    PubMed  Google Scholar 

  • Serreze DV, Chapman HD et al. (1996) B lymphocytes are essential for the initiation of T cellmediated autoimmune diabetes: Analysis of a new “speed congenic” stock of NOD.Ig mu(null) mice. J Exp Med 184(5):2049-2053

    PubMed  Google Scholar 

  • Serreze DV, Silveira PA (2003). The role of B lymphocytes as key antigen-presenting cells in the development of T cell-mediated autoimmune type 1 diabetes. Curr Dir Autoimmun 6:212-227

    PubMed  Google Scholar 

  • Shoda LK, Young DL et al. (2005) A Comprehensive Review of Interventions in the NOD Mouse and Implications for Translation. Immunity 23(2):115-126

    PubMed  Google Scholar 

  • Smith JA, Tang Q et al. (1998) Partial TCR signals delivered by FcR-nonbinding anti-CD3 monoclonal antibodies differentially regulate individual Th subsets. J Immunol 160(10):4841-4849

    PubMed  Google Scholar 

  • Smith JA, Tso JY et al. (1997) Nonmitogenic anti-CD3 monoclonal antibodies deliver a partial T cell receptor signal and induce clonal anergy. J Exp Med 185(8):1413-1422

    PubMed  Google Scholar 

  • Sreenan S, Pick AJ et al. (1999) Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48(5):989-996

    PubMed  Google Scholar 

  • Strandell E, Eizirik DL et al. (1990) Reversal of beta-cell suppression in vitro in pancreatic islets isolated from nonobese diabetic mice during the phase preceding insulin-dependent diabetes mellitus. J Clin Invest 85(6):1944-1950

    PubMed  Google Scholar 

  • Tisch R, Yang XD et al. (1994) Administering glutamic acid decarboxylase to NOD mice prevents diabetes. J Autoimmun 7(6):845-850

    PubMed  Google Scholar 

  • Trembleau S, Penna G et al. (1997) Deviation of pancreas-infiltrating cells to Th2 by interleukin-12 antagonist administration inhibits autoimmune diabetes. Eur J Immunol 27(9):2330-2339

    PubMed  Google Scholar 

  • Utsugi T, Yoon JW et al. (1996) Major histocompatibility complex class I-restricted infiltration and destruction of pancreatic islets by NOD mouse-derived beta-cell cytotoxic CD8(+) T-cell clones in vivo. Diabetes 45(8):1121-1131

    PubMed  Google Scholar 

  • Van Assche G, Van Ranst M et al. (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353(4):362-368

    PubMed  Google Scholar 

  • Van Lier RA, Boot JH et al. (1987) Induction of T cell proliferation with anti-CD3 switch-variant monoclonal antibodies: effects of heavy chain isotype in monocyte-dependent systems. Eur J Immunol 17(11):1599-1604

    PubMed  Google Scholar 

  • Vigeral P, Chkoff N et al. (1986) Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients. Utilization of OKT3 as the sole immunosuppressive agent. Transplantation 41 (6):730-733

    PubMed  Google Scholar 

  • Waldmann H, Cobbold S (1998) How do monoclonal antibodies induce tolerance? A role for infectious tolerance? Annu Rev Immunol 16:619-644

    PubMed  Google Scholar 

  • Wegmann DR (1996) The immune response to islets in experimental diabetes and insulindependent diabetes mellitus. Curr Opin Immunol 8(6):860-864

    PubMed  Google Scholar 

  • Wegmann DR, Norbury-glaser M et al. (1994) Insulin-specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD mice. Eur J Immunol 24(8):1853-1857

    PubMed  Google Scholar 

  • Wekerle T, Kurtz J et al. (2002) Mechanisms of transplant tolerance induction using costimulatory blockade. Curr Opin Immunol 14(5):592-600

    PubMed  Google Scholar 

  • Wesselborg S, Janssen O et al. (1993) Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells. J Immunol 150(10):4338-4345

    PubMed  Google Scholar 

  • Wicker LS, Miller BJ et al. (1986) Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes 35(8):855-860

    PubMed  Google Scholar 

  • Wong JT, Colvin RB (1991) Selective reduction and proliferation of the CD4+ and CD8+ T cell subsets with bispecific monoclonal antibodies: evidence for inter-T cell-mediated cytolysis. Clin Immunol Immunopathol 58(2):236-250

    PubMed  Google Scholar 

  • Wood ML, Monaco AP et al. (1971) Use of homozygous allogeneic bone marrow for induction of tolerance with antilymphocyte serum: dose and timing. Transplant Proc 3(1):676-679

    PubMed  Google Scholar 

  • Woodle ES, Xu D et al. (1999) Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3gamma1(Ala-Ala) in the treatment of acute renal allograft rejection. Transplantation 68(5):608-616

    PubMed  Google Scholar 

  • Yasunami R, Bach JF (1988) Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice. Eur J Immunol 18(3):481-484

    PubMed  Google Scholar 

  • Yasunami R, Debray-sachs M et al. (1990) Ontogeny of regulatory and effector T cells in autoimmune NOD mice. In: Shafrir E (eds) Frontiers in diabetes research. Lessons from animal diabetes III. vol 19, Smith-Gordon, London pp 88-93

    Google Scholar 

  • You S, Belghith M, et al. (2005) Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T cells. Diabetes 54:1415-1422

    PubMed  Google Scholar 

  • You S, Leforban B, et al. (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(15):6335-6340

    PubMed  Google Scholar 

  • You S, Thieblemont N, et al. (2006) Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol Rev 212:185-202

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Université René Descartes, Paris, France

    L. Chatenoud

  2. Institut National de la Santé et de la Recherche Médicale, Unité 580, Paris, France

    L. Chatenoud

  3. Hôpital Necker-Enfants Malades, 161 rue de Sèvres, 75743, Paris Cedex 15, France

    L. Chatenoud

Authors
  1. L. Chatenoud
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. ARC Chair of Rheumatology, Centre Lead Bone & Joint Research Unit, Queen Mary's School of Medicine & Dentistry John Vane Science Centre, Charterhouse Square, EC1M 6BQ, London, UK

    Yuti Chernajovsky

  2. Bone & Joint Research Unit, Queen Mary's School of Medicine & Dentistry John Vane Science Centre, Charterhouse Square, EC1M 6BQ, London, UK

    Ahuva Nissim

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Chatenoud, L. (2008). The Use of CD3-Specific Antibodies in Autoimmune Diabetes: A Step Toward the Induction of Immune Tolerance in the Clinic. In: Chernajovsky, Y., Nissim, A. (eds) Therapeutic Antibodies. Handbook of Experimental Pharmacology, vol 181. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73259-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation