Antigen-specific protection against graft-vs-host induced immune deficiency

A severe, antigen-nonspecific, and long-lasting immune-deficient state can be induced in healthy, adult immune-competent F1 hybrid mice by a single i.v. injection of parental T lymphocytes. The present report demonstrates that this graft-vs-host-induced immune deficiency (GVHID) can be prevented in an antigen-specific way by immunization of the F1 mice with allogeneic cells before induction of GVHID. Thus, spleen cells from (A X B)F1 mice primed with allogeneic cells from strain C and then injected with parental spleen cells from A did not generate cytotoxic T lymphocyte responses to trinitophenyl-modified self cells or to allogeneic cells from third party strains D or E. However, spleen cells from the same mice generated normal levels of cytotoxic T lymphocyte activity to allogeneic cells from C, the strain used for immunization. Furthermore, mice exposed to murine cytomegalovirus before induction of GVHID were resistant to a subsequent challenge with murine cytomegalovirus, whereas GVHID mice that received only the murine cytomegalovirus challenge all died. These findings are discussed with respect to the possibilities that primed and unprimed T helper cells may be differentially susceptible to the suppressive effects of GVH.