Diseases caused by reactions of T lymphocytes to in compatible structures of the major histocompatibility complex. I. Autoimmune hemolytic anemia

The capacities of various lymphoid cells from C57BL/10 donors to induce antibodies against red blood cells (RBC) in (C57BL/10 × DBA/2)F 1 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 lymphocytes in the induction of Coombs‐positive hemolytic anemia by the graft‐versus‐host reaction (GVHR). Since some of the anti‐RBC antibodies carried the Ig c allotype specific for the F 1 host, they were autoantibodies. When antibodies were eluted from the erythrocytes of F 1 mice undergoing the GVHR (GVH F 1 mice) and subsequently tested against normal RBC in the indirect Coombs' test, the Ig c allotype was demonstrable even on those antibodies found to react with RBC of the donor strain (C57BL/10). In addition, 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 (IgG 1 , IgG 2a , IgG 2b , IgA, and IgM). By means of histocompatibility typing it was shown that 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 F 1 mice Coombs‐positive erythrocytes were demonstrated for periods of more than 5 months; Ig c ‐positive anti‐RBC antibodies were detected for periods up to 3 months. When an additional injection of parental T cells was administered to GVH F 1 mice, which had become Coombs‐negative in the course of the GVHR, new anti‐RBC antibodies appeared. In contrast to F 1 B cells, T cells of the F 1 host were not needed for autoimmunization as shown by the induction of anti‐RBC auto‐antibodies in F 1 recipients that were depleted of autologous T cells prior to the administration of parental T cells. When (C57BL/10 × DBA/2)F 1 mice were back‐crossed into strain C57BL/10 and the offsprings injected with C57BL/10 (H‐2 bb ) lymphoid cells, most of the H‐2 heterozygous (H‐2 bd ) back‐crosses developed Coombs'‐positive hemolytic anemia, whereas none of the H‐2 homozygous (H‐2 bb ) ones did. The most likely explanation of these results is that anti‐RBC autoantibodies were induced by a persistent reaction of parental T helper cells to incompatible H‐2 structures on normally present autoreactive F 1 B cells. The hypothesis is proposed that reactions of T lymphocytes against virally or chemically altered structures of the major histocompatibility complex may lead to autoimmunization also in non chimeric individuals.