Absence of correlation between cytolytic T lymphocytes and lethal murine graft-versus-host disease in response to minor histocompatibility antigens

Lethally irradiated mice were transplanted with bone marrow plus spleen cells from H-2 identical donor mice. Five of the six recipient strains developed lethal GVHD, but the sixth strain did not develop any signs of GVHD. Spleen cells from all six transplanted strains were cytotoxic to recipient strain target cells in a short-term chromium release assay. The cytotoxic spleen cells were antigen-specific for recipient strain target cells, Thy-1+ and Lyt-2+--and some were also Lyt-1+. These data demonstrate for the first time that the presence of antirecipient cytotoxic T lymphocytes (CTL) does not correlate with lethal GVHD. Although CTL may contribute to the pathogenesis of GVHD in response to minor histocompatibility antigens, they do not appear to be the primary effector mechanism.