T cell activation in the presence of cyclosporine in three in vivo allograft models.
The effect of cyclosporine on a systemic graft-versus-host reaction, cardiac allograft rejection, and a local host-versus-graft reaction in the rat were examined in detail. Therapeutic levels of CsA did not inhibit the early stages of lymphocyte activation but did prevent maturation of the immune response to full effector function--viz., graft rejection or clinical GVH disease. In all three models the phenotype changes in T cells associated with the early stages of activation--i.e., induction of receptors for interleukin 2 (IL-R), induction of MHC class II expression, and coexpression of CD4 and CD8 glycoproteins--were not inhibited by CsA. In the GVH and HVG reactions lymphocyte activation proceeded as far as DNA synthesis. In the systemic GVH model animals showed no sign of GVHD for as long as CsA was administered, but withdrawal of the drug resulted in accelerated lethal GVHD.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D003524:Cyclosporins / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects; D006086:Graft vs Host Disease / Q000276:immunology; D016027:Heart Transplantation; D006789:Host vs Graft Reaction / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins