Induction of tolerance in freshly isolated alloreactive T cells by activated T cell stimulators is not due to the absence of CD28-B7 interaction.
Human T cells express MHC class II molecules on activation, and this makes them potential APCs for responder CD4 T cells. We have shown earlier that MHC class II-expressing human T cell APCs induce specific tolerance in freshly isolated alloreactive responder CD4 T cells. In this study, we show that this induction of tolerance does not depend on the expression of a specific coreceptor on the stimulator T cell APCs, because both CD4 and CD8 T cell stimulators efficiently induce tolerance. Such a tolerant cell population responds significantly better to IL-2 than unprimed cells, indicating the physical presence of T cells expressing higher levels of IL-2 receptors. The addition of exogenous IL-2 during priming with activated T cell APCs effectively blocks the induction of tolerance and permits successful priming of alloreactive responder cells. We have investigated the possible role of the CD28/CTLA4-B7 family interaction in this model of induction of T cell anergy in T-T interactions. The freshly activated T cell APCs used in this study express CTLA4-binding ligand(s). Furthermore, cross-linking CD28 on responder T cells does not enable activated T cell APCs to elicit a primary proliferative alloresponse, nor does it prevent the induction of tolerance in responder T cells. The CD28/CTLA4-B7 family interaction is thus unlikely to be involved in the induction of T cell anergy by T cell APCs.
Satyaraj
E
E
National Institute of Immunology, New Delhi, India.
Rath
S
S
Bal
V
V
D017951:Antigen Presentation; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation
D018106:CD28 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2