Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F 1 → C3H chimeras: Evidence for host-versus-graft reaction initiated by radioresistant T cells

Abstract

Lethally irradiated C3Hf mice reconstituted with a relatively low dose (2 × 10 6) of B6C3F 1 bone marrow cells (B6C3F 1 → C3Hf chimeras) frequently manifest immunohematologic deficiencies during the first month following injection of bone marrow cells. They show slow recovery of antibody-forming potential to sheep red blood cells (SRBC) as compared to that observed in syngeneic (C3Hf → C3Hf or B6C3F 1 → B6C3F 1) chimeras. They also show a deficiency of B-cell activity as assessed by antibody response to SRBC following further reconstitution with B6C3F 1-derived thymus cells 1 week after injection of bone marrow cells. A significant fraction of B6C3F 1 → C3Hf chimeras was shown to manifest a sudden loss of cellularity of spleens during the second week following injection of bone marrow cells even though cellularity was restored to the normal level within 1 week. The splenic mononuclear cells recovered from such chimeras almost invariably showed strong cytotoxicity against target cells expressing donor-type specific H-2 antigens (H-2 b) when assessed by 51Cr-release assay in vitro. The effector cells responsible for the observed anti-donor specific cytotoxicity were shown to be residual host-derived T cells. These results indicate strongly that residual host T cells could develop anti-donor specific cytotoxicity even after exposure to a supralethal dose (1050 R) of radiation and that the immunohematologic disturbances observed in short-term F 1 to parent bone marrow chimeras (B6C3F 1 → C3Hf) were due to host-versus-graft reaction (HVGR) initiated by residual host T cells. The implication of these findings on the radiobiological nature of the residual T cells and the persistence of potentially anti-donor reactive T-cell clones in long-surviving allogeneic bone marrow chimeras was discussed.