Genetic and cellular aspects of xenogeneic mixed leukocyte culture reaction.

Abstract

The nature of the antigens stimulating xenogeneic lymphocytes was studied using primed LD [lymphocyte determined antigen] typing. Human lymphocytes were sensitized in vitro against mouse spleen cells and restimulated with spleen cells of mouse strains sharing non-H-2 antigens or various regions of H-2 with the initial stimulating strain. The largest thymidine uptake was caused by restimulation with cells from the specific primary stimulator or an H-2-identical strain. Species-specific antigens or strain-specific antigens carried in the C57BL/10 background account for less than 15% of the total stimulation; a non-H-2 antigen associated with the Mlsa genotype caused moderate restimulation, amounting to 25% of the average H-2 response, Within H-2 the strongest restimulation was caused by antigens controlled by the I-A subregion, the K and D regions caused moderate, the I-C and S regions very weak, and the I-B subregion no restimulation. The genetic control of antigens stimulating xenogeneic and allogenic MLC [mixed leukocyte culture] responses appears identical. Like an allogenic MLC reaction, the xenogeneic MLC response requires T [thymus-derived] cells and adherent cells, but in the human-mouse MLC, both cell types must come from the human responder; the majority of the proliferating cells are T cells. It is suggested that allograft and xenograft reactions are fundamentally identical processes, and that the relative vigor of alloaggression may be explained by secondary potentiating mechanisms depending on species-specific interactions between aggressor and target cells.