Development of graft-vs.-host disease-like syndrome in cyclosporine- treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity

The effector cell in our studies was shown to be a T lymphocyte of the OX8 phenotype, a marker for non-T helper cells in the rat. This data is compatible with the observations of Glazier et al. (15, 21) , and Cheney and Sprent (23) , who demonstrated that the syngeneic GVHD-like syndrome could be adoptively transferred into irradiated syngeneic recipients. Although there was a highly significant association of syngeneic GVHD with the development of anti-Iaspecific cytotoxic T cells, it remains unknown whether these cells are the mediators of this syndrome or require other interacting T cell-subsets. Studies are currently underway to adoptively transfer syngeneic GVHD by transferring cell populations enriched for this killer T cell. In the studies of Cheney and Sprent (23) using a murine model of CsA-induced syngeneic GVHD, a striking decrease in overall thymic Ia expression was observed, compared to control transplanted animals. The results of our studies could explain their findings, in that the anti-Ia cytotoxic T cells eliminated the cells bearing the class II antigens. It may also be, that in syngeneic GVHD, reduced thymic Ia expression resulted in a failure of T lymphocyte maturation, with the subsequent induction of Ia° specific cytotoxic T cells.