DISEASES CAUSED BY REACTIONS OF T LYMPHOCYTES TO INCOMPATIBLE STRUCTURES OF MAJOR HISTOCOMPATIBILITY COMPLEX .1. AUTOIMMUNE HEMOLYTIC-ANEMIA

The capacities of various lymphoid cells from C57BL/10 [mouse] donors to induce antibodies against red blood cells (RBC) in (C57BL/10 .times. DBA/2)F1 recipients were compared: cortisone-resistant thymocytes were more potent inducers than spleen cells, and bone marrow cells were ineffective. This established a need for parental T [thymus-derived] lymphocytes in the induction of Coombs-positive hemolytic anemia by the graft-vs.-host reaction (GVHR). Since some of the anti-RBC antibodies carried the Ig[immunoglobulin]c allotype specific for the F1 host, they were autoantibodies. When antibodies were eluted from the erythrocytes of F1 mice undergoing the GVHR (GVH F1 mice) and subsequently tested against normal RBC in the indirect Coombs'' test, the Igc allotype was demonstrable even on those antibodies reacting with RBC of the donor strain (C57BL/10). Reactions with normal intact RBC of other strains and species were noted. Anti-RBC antibodies belonged to all Ig classes and subclasses that were tested (IgG1, IgG2a, IgG2b, IgA and IgM). The overwhelming majority of lymphoid cells from GVH animals were host cells; most of these host cells were Thy-1.2-negative. In several GVH F1 mice, Coombs-positive erythrocytes were demonstrated for periods of more than 5 mo.; Igc-positive anti-RBC antibodies were detected for periods up to 3 mo. When an additional injection of parental T cells was administered to GVH F1 mice, which had become Coombs-negative in the course of the GVHR, new anti-RBC antibodies appeared. In contrast to F1 B [bone marrow-derived] cells, T cells of the F1 host were not needed for autoimmunization. When (C57BL/10 .times. DBA/2)F1 mice were back-crossed into strain C57BL/10 and the offsprings injected with C57BL/10 (H-2bb) lymphoid cells, most of the H-2 heterozygous (H-2bd) back-crosses developed Coombs''-positive hemolytic anemia; none of the H-2 homozygous (H-2bb) ones did. Anti-RBC autoantibodies were probably induced by a persistent reaction of parental T helper cells to incompatible H-2 structures on normally present autoreactive F1 B cells. Reactions of T lymphocytes against virally or chemically altered structures of the major histocompatibility complex may lead to auto-immunization in nonchimeric individuals also.