Effect of T cell and alloantibody regulatory interactions on the immune responses stimulated by rat major and minor alloantigens.

Six inbred rat strains were immunized with rat cells differing both by antigens coded at the major (AgB or H-1) locus and by antigens coded at minor loci. Other animals of these six strains were immunized with cells which differed only by minor loci coded antigens. The complement dependent cytotoxin and the direct cytotoxic lymphocyte responses to these two types of antigenic disparities were measured and compared. The complement dependent cytotoxins in antisera elicited by multiple major and minor antigen stimulation (major disparity antisera) were high tittered and were able to kill 100% of available target lymphocytes over a wide series of dilutions. Antisera elicited by minor antigens (minor disparity antisera) showed titration endpoints equally as high as the major disparity antisera. However, no concentration was able to kill 100% of available target lymphocytes. Homologous absorption detected a 10-fold higher concentration of total antibody in the minor disparity antisera than in major disparity antisera. These studies also established the presence in the minor disparity antisera of large component of specific non-complement fixing antibody. Minor and major alloantigens were comparable in their ability upon injection to evoke lymphocytes capable a mediating “in vivo†lysis of fibroblast carrying the sensitizing antigens Major and minor disparity antisera were compared for their ability to inhibit this cell mediated cytotoxicity (CMC). Minor disparity antisera inhibited CMC while major disparity antisera did not. Minor disparity antisera also had enhancing antibody activity as measured by the antisera’s ability to passively prolong fetal heart grafts placed in recipient’s ears. The prolongation was immuno-specific. Inbred rats were neonatally thymectomized and challenged as adults with cells carrying either major or minor antigenic disparities. In contrast, thymectomized rats challenged with cells differing only by minor antigens failed to produce complement dependent cytotoxins. These animals were also unable to produce antibody with CMC inhibitory activity. The data can be interpreted to mean that minor alloantigens elicit antibody with suppress T-cell. This antibody could be immuno-regulatory. This could mean that minor alloantigens elicit immuno-regulatory antibody preferentially over other types of antibody. The production of these regulatory antibodies requires T-cell cooperation. The apparent reduced immunogenicity of minor alloantigens when stimulating mixed lymphocyte blastogenesis, graft vs. host reaction, and organ graft rejection may be the result of T-cell suppression by regulatory antibody.