Progress towards the clinical use of CD3 monoclonal antibodies  in the treatment of autoimmunity.
OBJECTIVE
A major problem in the field of clinical transplantation, as well as in autoimmunity, is that conventional treatments rely on chronic immunosuppression that is not specific for the antigens involved and that increases the risk of infections and tumours. A major need and challenge is, therefore, to achieve 'operational tolerance', namely an inhibition of pathogenic responses in the absence of chronic immunosuppression.


RESULTS
Here we review data showing that monoclonal antibodies to the CD3 complex, the signal transducing element of the T cell receptor, promote immune tolerance. This strategy has been the matter of extensive experimental studies in models of autoimmunity and has recently led to a successful clinical translation.


CONCLUSIONS
Results from controlled trials in autoimmune insulin-dependent diabetes showed that CD3 monoclonal antibodies afford long-term effects following a short administration. The present challenge is to build on these results, first, to set the use of CD3 monoclonal antibodies as an established therapy in well selected subsets of patients with autoimmunity, and second, given the similarities of immune mechanisms underlying T cell-mediated autoimmune diseases and allograft rejection, to address if and how this therapeutic strategy could be extended to organ transplantation in the not-too-distant future.
Chatenoud
Lucienne
L
Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale, Unité 580, Hôpital Necker, Paris, France. lucienne.chatenoud@inserm.fr
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D017252:CD3 Complex / Q000276:immunology*; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D023001:Transplantation Tolerance / Q000187:drug effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007166:Immunosuppressive Agents