Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice.

Author information

Affiliations

  • 1. Institut National de la Santé et de la Recherche Médicale U 25, Hôpital Necker, Paris, France.
      Authors
    • Chatenoud L 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Jan 1994, 91(1):123-127
https://doi.org/10.1073/pnas.91.1.123 PMID: 8278351 PMCID: PMC42898

Free full text in Europe PMC

Abstract 

Anti-CD3 monoclonal antibodies suppress immune responses by transient T-cell depletion and antigenic modulation of the CD3/T-cell receptor complex. Anti-CD3 treatment of adult nonobese diabetic (NOD) mice, a spontaneous model of T-cell-mediated autoimmune insulin-dependent diabetes mellitus, significantly inhibits the autoimmune process. Short-term low-dose anti-CD3 treatment (5 micrograms/day i.v. for 5 consecutive days) prevented the occurrence of an accelerated form of the disease induced by cyclophosphamide. More unexpectedly, when applied to adult NOD females within 7 days of the onset of full-blown diabetes, the same anti-CD3 regimen induced a complete remission of overt disease (i.e., a return to permanent normoglycemia) in 64-80% of mice. This remission was durable (> 4 months) and was not associated with the disappearance of insulitis (mononuclear cell infiltration of the islets). The immunosuppression was apparently specific for beta-cell-associated antigens, since mice showing anti-CD3-induced remission rejected histoincompatible skin grafts normally, whereas they did not destroy syngeneic islet grafts, unlike control untreated overtly diabetic NOD females. These results open major therapeutic perspectives. They strongly suggest that self-tolerance can be restored in adult mice once autoimmunity is fully established and confirm that this effect can be obtained by transient targeting of the CD3/T-cell receptor without massive T-cell debulking.

Free full text 

Logo of pnasLink to Publisher's site
Proc Natl Acad Sci U S A. 1994 Jan 4; 91(1): 123–127.
PMCID: PMC42898
PMID: 8278351

Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice.

L Chatenoud, E Thervet, J Primo, and J F Bach
Author information Copyright and License information Disclaimer

Abstract

Anti-CD3 monoclonal antibodies suppress immune responses by transient T-cell depletion and antigenic modulation of the CD3/T-cell receptor complex. Anti-CD3 treatment of adult nonobese diabetic (NOD) mice, a spontaneous model of T-cell-mediated autoimmune insulin-dependent diabetes mellitus, significantly inhibits the autoimmune process. Short-term low-dose anti-CD3 treatment (5 micrograms/day i.v. for 5 consecutive days) prevented the occurrence of an accelerated form of the disease induced by cyclophosphamide. More unexpectedly, when applied to adult NOD females within 7 days of the onset of full-blown diabetes, the same anti-CD3 regimen induced a complete remission of overt disease (i.e., a return to permanent normoglycemia) in 64-80% of mice. This remission was durable (> 4 months) and was not associated with the disappearance of insulitis (mononuclear cell infiltration of the islets). The immunosuppression was apparently specific for beta-cell-associated antigens, since mice showing anti-CD3-induced remission rejected histoincompatible skin grafts normally, whereas they did not destroy syngeneic islet grafts, unlike control untreated overtly diabetic NOD females. These results open major therapeutic perspectives. They strongly suggest that self-tolerance can be restored in adult mice once autoimmunity is fully established and confirm that this effect can be obtained by transient targeting of the CD3/T-cell receptor without massive T-cell debulking.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
 
icon of scanned page 123
123
icon of scanned page 124
124
icon of scanned page 125
125
icon of scanned page 126
126
icon of scanned page 127
127
 

Images in this article

Fig. 1
Fig. 1
on p.124
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Castaño L, Eisenbarth GS. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol. 1990;8:647–679. [Abstract] [Google Scholar]
  • Hayward AR, Shreiber M. Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes. J Immunol. 1989 Sep 1;143(5):1555–1559. [Abstract] [Google Scholar]
  • Bendelac A, Carnaud C, Boitard C, Bach JF. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J Exp Med. 1987 Oct 1;166(4):823–832. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shizuru JA, Taylor-Edwards C, Banks BA, Gregory AK, Fathman CG. Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes. Science. 1988 Apr 29;240(4852):659–662. [Abstract] [Google Scholar]
  • Charlton B, Bacelj A, Mandel TE. Administration of silica particles or anti-Lyt2 antibody prevents beta-cell destruction in NOD mice given cyclophosphamide. Diabetes. 1988 Jul;37(7):930–935. [Abstract] [Google Scholar]
  • Hutchings P, Rosen H, O'Reilly L, Simpson E, Gordon S, Cooke A. Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Nature. 1990 Dec 13;348(6302):639–642. [Abstract] [Google Scholar]
  • Sempé P, Bédossa P, Richard MF, Villà MC, Bach JF, Boitard C. Anti-alpha/beta T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice. Eur J Immunol. 1991 May;21(5):1163–1169. [Abstract] [Google Scholar]
  • Boitard C, Yasunami R, Dardenne M, Bach JF. T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice. J Exp Med. 1989 May 1;169(5):1669–1680. [Europe PMC free article] [Abstract] [Google Scholar]
  • Qin SX, Cobbold S, Benjamin R, Waldmann H. Induction of classical transplantation tolerance in the adult. J Exp Med. 1989 Mar 1;169(3):779–794. [Europe PMC free article] [Abstract] [Google Scholar]
  • Qin S, Cobbold SP, Pope H, Elliott J, Kioussis D, Davies J, Waldmann H. "Infectious" transplantation tolerance. Science. 1993 Feb 12;259(5097):974–977. [Abstract] [Google Scholar]
  • Pearson TC, Madsen JC, Larsen CP, Morris PJ, Wood KJ. Induction of transplantation tolerance in adults using donor antigen and anti-CD4 monoclonal antibody. Transplantation. 1992 Sep;54(3):475–483. [Abstract] [Google Scholar]
  • Leo O, Foo M, Sachs DH, Samelson LE, Bluestone JA. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gotoh M, Maki T, Satomi S, Porter J, Bonner-Weir S, O'Hara CJ, Monaco AP. Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection. Transplantation. 1987 May;43(5):725–730. [Abstract] [Google Scholar]
  • Cobbold SP, Jayasuriya A, Nash A, Prospero TD, Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. [Abstract] [Google Scholar]
  • Chatenoud L, Baudrihaye MF, Kreis H, Goldstein G, Schindler J, Bach JF. Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur J Immunol. 1982 Nov;12(11):979–982. [Abstract] [Google Scholar]
  • Ferran C, Sheehan K, Dy M, Schreiber R, Merite S, Landais P, Noel LH, Grau G, Bluestone J, Bach JF, et al. Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation. Eur J Immunol. 1990 Mar;20(3):509–515. [Abstract] [Google Scholar]
  • Ferran C, Dy M, Sheehan K, Merite S, Schreiber R, Landais P, Grau G, Bluestone J, Bach JF, Chatenoud L. Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release. Clin Exp Immunol. 1991 Dec;86(3):537–543. [Abstract] [Google Scholar]
  • Yasunami R, Bach JF. Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice. Eur J Immunol. 1988 Mar;18(3):481–484. [Abstract] [Google Scholar]
  • Charlton B, Bacelj A, Slattery RM, Mandel TE. Cyclophosphamide-induced diabetes in NOD/WEHI mice. Evidence for suppression in spontaneous autoimmune diabetes mellitus. Diabetes. 1989 Apr;38(4):441–447. [Abstract] [Google Scholar]
  • Herold KC, Bluestone JA, Montag AG, Parihar A, Wiegner A, Gress RE, Hirsch R. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes. 1992 Mar;41(3):385–391. [Abstract] [Google Scholar]
  • Campos HH, Bach JF, Chatenoud L. Devising murine models to better adapt clinical protocols: sequential low-dose treatment with anti-CD3 and anti-CD4 monoclonal antibodies to prevent fully mismatched allograft rejection. Transplant Proc. 1993 Feb;25(1 Pt 1):798–799. [Abstract] [Google Scholar]
  • Maki T, Ichikawa T, Blanco R, Porter J. Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3434–3438. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shah SC, Malone JI, Simpson NE. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med. 1989 Mar 2;320(9):550–554. [Abstract] [Google Scholar]
Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Full text links 

Read article at publisher's site: https://doi.org/10.1073/pnas.91.1.123

Read article for free, from open access legal sources, via Unpaywall: http://www.pnas.org/content/91/1/123.full.pdfUnpaywall

Citations & impact 

Impact metrics

405
Citations
Jump to Citations
1
Data citation
Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/35534763
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/35534763

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1073/pnas.91.1.123

Supporting
Mentioning
Contrasting
26
441
1

Article citations

Go to all (405) article citations

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.