Title
In-vivo immunosuppression induced by a weakly mitogenic antibody to mouse cd3 : evidence that induction of long-lasting in-vivo unresponsiveness requires tcr signaling
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
New York ,
Subject
Biology
Human medicine
Source (journal)
Cellular immunology. - New York
Volume/pages
157(1994) :1 , p. 239-248
ISSN
0008-8749
ISI
A1994NZ09300020
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
The use of anti-CD3 monoclonal antibodies (mAb) to treat allograft rejection has been complicated by the morbidity observed during the first days of treatment, secondary to T cell activation and cytokine release. Available evidence in a mouse model indicates that F(ab')(2) fragments of an anti-CD3 mAb are not mitogenic in vitro and can be injected in vivo without apparent toxicity. However, their immunosuppressive capacity is dramatically reduced, suggesting that long-term immunosuppression mediated by anti-CD3 antibodies in vivo may be associated to their mitogenic capacity. This paper demonstrates that a poorly mitogenic anti-CD3 mAb is able to induce potent immunosuppression in vivo with reduced morbidity. This finding suggests that immunosuppression in vivo by anti-CD3 mAbs is not directly related to their activation properties but nevertheless requires signaling capacities. Therefore, immunosuppression in vivo may be best achieved by using antibodies able to deliver an incomplete activation signal to T cells (thus avoiding systemic cytokine release), possibly leading to anergy. The implications of this study for the development of immunosuppressive antibodies are discussed. (C) 1994 Academic Press, Inc.
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