Incompatibility at irrelevant H-2 specificities augments in vivo stimulation of alloaggressive cells

Abstract

Lymphoid cells of mice were sensitized in vivo either by H-2 strain-specific tumor allografts or by activation in lethally irradiated F1 hybrids and tested for cytotoxicity on 51Cr-labeled target cells. The release of 51Cr varied linearly with the logarithm to the proportion of effector lymphocytes to target cells and with the time of interaction. The release of 51Cr was immunologically specific and restricted to H-2 incompatibility. Spleen cells immune to public specificities of the target genotype were not cytotoxic. However, lymphoid cells immune to only one private specificity of a third-party target genotype were highly cytotoxic. The cytotoxicity of activated thymus cells on target cells sharing one private specificity with the genotype used for sensitization was significantly enhanced when the effector thymocytes were activated also against H-2 specificities not shared by the target strain. The results suggest that gene products that facilitate sensitization of effector cells may be determined both by the H-2K and the H-2D end of the H-2 complex. It remains to be shown whether the products of these loci, operating during sensitization in vivo, are body-wide correlated to the lymphocyte-defined specificities detectable during the mixed leukocyte culture interaction.