Acquisition of graft-versus-host reactivity by immature thymocytes in the coexistence of activated macrophages.

The collaborative role of macrophages in the acquisition of the rat graft-versus-host (GVH) reactivity by parental thymocytes was investigated by the popliteal lymph node enlargement assay. The addition of peritoneal macrophages activated by streptococcal bacteria injection resulted in significantly increased GVH reactivity of parental thymocytes, when assayed both in normal F1 hybrid hosts and in those depleted of effective macrophages and lymphocytes. The thymocytes that acquire that alloantigen reactivity in the presence of activated macrophages were shown to be cortisone sensitive and of high density. Hence, the cortisone-resistant and less dense population of thymocytes did not exhibit further reactivity even in the presence of macrophages; however, this subpopulation showed an enriched activity on its own. Moreover, the simultaneous injection of activated macrophages induced a further augmenting effect on the graft-versus-host reaction (GVHR) of freshly peripheralized thymocytes, but did not affect the reactivity of lymph lymphocytes from parental rats thymectomized 15 months previously. These data suggest that activated macrophages play an essential role in the acquisition of alloantigen reactivity by immature thymocytes, and also that the macrophage-dependent thymocytes in the reaction may reside among the subpopulation that is cortisone sensitive, highly dense, short-lived, and freshly peripheralized. The possible nature of immunological maturation of immature thymocytes in the periphery is discussed in relation to cellular interactions with activated macrophages.