• Citer

Induction of T cell unresponsiveness by anti-CD3 antibodies occurs independently of co-stimulatory functions

par Andris, Fabienne ;Van Mechelen, Marcelle ;De Mattia, Fabrizio ;Baus, Erika ;Urbain, Jacques ;Leo, Oberdan
Référence European Journal of Immunology, 26, 5, page (1187-1195)
Publication Publié, 1996-05

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

Antibodies to the T cell receptor (TcR)-associated CD3 molecules represent potent immunosuppressive agents in vivo in both human and animals models, in spite of their well-characterized mitogenic properties. We demonstrate in this report that antibodies to the B7.2 molecule inhibit IL-2 production in vivo caused by anti-CD3 administration, suggesting that anti-CD3 monoclonal antibodies (mAb) stimulate naive T cells in vivo in a co-stimulation-dependent fashion. To characterize better the mechanisms by which antibodies to CD3 induce antigen unresponsiveness in naive T cells, we developed a model of activation-induced T cell unresponsiveness in vitro. Our data indicate that following interaction with mitogenic anti-CD3 mAb in vitro, naive purified CD4+ T cells become refractory to a further stimulus. This unresponsive state develops independently of co-stimulatory functions, as neither B7-expressing antigen-presenting cells nor anti-CD28 mAb are able to prevent anergy induction in this model. We therefore conclude that induction of unresponsiveness in naive T cells by anti-CD3 mAb is not a consequence of co-stimulus-deficient stimulation, but may develop following a productive response both in vivo and in vitro. Unresponsive T cells display a defective calcium mobilization upon TcR triggering, suggesting that anergy is maintained in these cells through receptor desensitization. The potential role of co-stimulation-independent TcR desensitization in the down-regulation of immune responses in vivo is briefly discussed.