Anti-CD4 induced rat heart tolerance: no presence of primed T cells and regulatory mechanisms for cytotoxic T cells

Treatment with anti-CD4 monoclonal antibody (mAb) (OX38) induces heart, but not skin graft tolerance in WF (RT1(0)) to Lewis (RT1(1)) rat strain combi nations. We examined differences in cellular responses between heart-bearin g and skin-rejected hosts that were both treated with anti-CD4 mAb. In the tolerant LEW rats bearing WF heart transplants, the secondary WF heart but not skin grafts were accepted. On the other hand, in anti-CD4 treated WF sk in-rejected hosts, both secondary WF heart and skin grafts were rapidly rej ected. Spleen cells from anti-CD4 treated WF skin-rejected LEW rats but not from WF heart-bearing LEW rats received the same treatment generated CTL a fter in vitro stimulation with paraformaldehyde (PFA) treated donor WF stim ulator spleen cells. Adoptive transfer of spleen cells from WF skin-rejecte d LEW rats with or without anti-CD4 therapy into the tolerant LEW rats at t he secondary WF heart transplantation blocked the secondary heart graft acc eptance. However, transfer of spleen cells from WF heart-rejected rats with out immunosuppression failed to block acceptance of the secondary heart gra ft. Our results indicated the lack of primed T cells and presence of regula tory mechanisms for tissue specific T cells in anti-CD4 treated heart beari ng hosts. (C) 2000 Elsevier Science B.V. All rights reserved.