Experimental stimulation of cell-mediated immunity without concomitant stimulation of humoral immunity in graft-versus-host immunosuppressed mice

The immunosuppressive effect of the graft-versus-host (GVH) reaction was studied in CBA X A F1 (CAF1) mice which had been rendered immunologically unresponsive by the injection of parental A strain lymphoid cells (GVH mice). Suppression of both cell-mediated and humoral immune responses was demonstrated by the prolonged survival of C57BL/6 (B6) skin allografts and by the inability of GVH mice to produce detectable antibody following stimulation with sheep erythrocytes (SRBC). Appropriate stimulation of GVH mice induced cell-mediated immune reactions to xeno- and allogeneic antigens while the humoral immune responses to the same antigens remained suppressed. Multiple challenges of the GVH mice with B6 tissue caused a rapid rejection of subsequent B6 skin grafts but failed to stimulate the production of any detectable antibodies to B6 allotransplantation antigens. Sensitization of GVH mice with SRBC in Freund's complete adjuvant stimulated a delayed hypersensitivity response to SRBC, although no humoral response to SRBC could be detected, even after three challenges with SRBC. The experimental results are discussed in terms of a proposed model for GVH-induced immunosuppression.