Inhibition of antisuppression by the acute murine graft-versus-host reaction

Profound suppression of both humoral and cell-mediated immunity is a significant systemic effect of graft-versus-host reactions. Although no complete explanation has been advanced for this immunosuppression suppressor cells have been implicated. The data presented in this paper indicate that acute GVH reactions in (C57BL/6J X A/J) F1-hybrid mice induced by the injection of A/J cells severely disrupts the function of the antisuppressor T-cell pathway at both its induction and effector stages. Results show that within 3 weeks of induction of the reaction, Ly1+-T antisuppressor inducer cells lose their ability to generate the serum factor that mediates antisuppression. This factor is normally taken up by and activates Ly2+ T cells which then inhibit suppressor T-cell function. The data also reveal that Ly2+ T cells collected 2 weeks after induction lose their ability to be activated by the antisuppressor factor produced in normal mice. These cells are thus unable to function as antisuppressor effector cells. The uptake of the antisuppressor factor by Ly2+ T cells depends on the expression of Ia antigens on the surface of these cells. Experiments have shown that these antigens are absent from the surface of T cells derived from mice with GVH reactions. This finding may provide an explanation for the inability of these cells to function as antisuppressor effectors. Antisuppression is an important T-cell pathway that is intimately associated with the regulation of immune function. It is possible that the immunosuppression arising in mice with GVH reactions may stem, in part, from unopposed suppressor T-cell activity that results from widespread interference by the reaction with a pathway that normally inhibits suppressor cell activity.