Graft-versus-host reaction-induced immune modulation. I. Donor-recipient genetic disparity and the differential expression of Lyt-2, L3T4, and Ly-6 during acute reactions in the host thymus.

To investigate the effects of graft-vs-host reactions (GvHR) on cells in a central lymphoid compartment, GvHR were induced across class I/II or class II only major histocompatibility complex differences utilizing the parent into nonirradiated F1 hybrid (P----F1) model. Thymocytes were subsequently examined during the acute stage of GvHR for the expression of Lyt-2, L3T4, and Ly-6 cell surface molecules. Class I/II "suppressive" GvHR resulted in a dramatic decrease (greater than 85%) in total thymocyte numbers by 2 wk after parental cell injection. Although a dramatic decrease in the percentages of Lyt-2 (85%----30%) and L3T4 (95%----50%) expression was observed, the percentage of thymocytes expressing Ly-6 was markedly increased compared to uninjected controls (5%----greater than 80%). This increased percentage was not due solely to a selective loss of Ly-6 negative cells from the thymus, since the actual number of Ly-6 positive cells was greater in GvHR mice than in controls. Class II GvHR during the same time interval resulted in a less dramatic decrease (20 to 60%) in total thymocyte numbers. In addition, the effect on the percentages of Lyt-2 (85%----approximately 70%) and L3T4 (95%----approximately 85) expression was subtle and transient. However, intrathymic Ly-6 expression was again clearly enhanced (5%----20 to 30%). Class I/II "proliferative" or "stimulatory" GvHR differ from "suppressive" reactions in that they are characterized by stimulatory pathologic symptoms and the appearance of autoimmune abnormalities. Such GvHR were found to result in minimal alteration of total thymocyte numbers. Similarly, the percentage expression of Lyt-2 and L3T4 was marginally affected. However, the percentage of Ly-6 expression was increased from 5%----20 to 30% and thus these intrathymic lymphocyte profiles more closely resemble those of class II as compared to class I/II "suppressive" GvHR. The present findings therefore demonstrate that major histocompatibility complex differences alone do not necessarily determine the effects of GvHR on recipient thymocytes and that Ly-6 is a useful marker for the early detection of GvHR-associated immunologic events.