The Mixed Lymphocyte Reaction: an in Vitro Test for Tolerance

Tolerance, as defined by an inability to produce runt disease and the failure to elicit a normal lymphocyte transfer reaction, was induced in Lewis and Brown Norway rats by the neonatal injection of bone marrow from the opposite strain. When thymus, thoracic duct lymph, or lymph node cells from such tolerant Lewis and Brown Norway rats were cultured together, or were individually cultured with similar cells from an F(1) hybrid of these strains, transformation was suppressed to the levels observed in nonmixed control cultures. In contrast, mixtures of cells involving nontolerant donors demonstrated significant transformation as measured by per cent enlarged cells and thymidine-(3)H uptake. The specificity of the tolerance was confirmed by the presence of transformed cells in mixtures involving cells from a tolerant donor and an unrelated or a partially related third strain of rats. From these results, it is suggested that the mixed lymphocyte reaction may be used as a simple test for tolerance and that it most likely represents an in vitro immune response.