DISSOCIATION OF TISSUE DESTRUCTION INDUCED BY CYTOLYTIC T-CELLS INVIVO AND CYTOTOXICITY AS MEASURED INVITRO

Two forms of local cutaneous graft-versus-host reactions were used to examine the in vivo activity of cytolytic T cells in a large number of antigen systems and mouse strain combinations. In immune lymphocyte transfer reactions (TrRs), CTL were injected intrader- mally into allogeneic hosts to which they were sensitized; in bystander reactions (ByRs), CTL were mixed with target cells and the mixture injected into hosts syngeneic to the CTL. Both reactions frequently culminate in full-thickness skin destruction. However, CTL highly active in cell-mediated lympholysis assays in vitro sometimes failed to induce significant reactions in vivo, and CTL with negligible CML activity often induced severe, necrotizing lesions. In addition, Clone 58, a non-MHC-specific CD8+ clone that originated from cells extracted from a sponge matrix allograft, lost its CML activity but continued to induce necrotizing TrRs and ByRs. Insofar as these reactions may exemplify the specific (TrR) and nonspecific (ByR) tissue injury that occurs in the rejection process, these findings question the reliability of CML for predicting the ability of CTL to induce the tissue destruction seen in allograft rejection. © 1990 by Williams & Wilkins.