Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient XXXX grafts.

@entity19 @entity5 @entity706 @entity8200
@entity8200 -deficient variants, selected from the @entity19 @entity706 , were recently shown to be less tumorigenic in syngeneic @entity19 compared with the corresponding @entity8200 -positive wild-type cell line. The present study focused on the detailed cellular interactions leading to the specific rejection of @entity8200 -deficient cells in vivo. In vivo experiments with @entity5 inocula, measuring either @entity5 outgrowth or rapid elimination, showed that the presence of @entity8200 -positive @entity706 cells did not suppress the rejection of @entity8200 -deficient cells. Conversely, @entity8200 -deficient cells did not activate a rejection of @entity8200 -positive cells. @entity8200 -deficient cells were selectively eliminated even when they were present in a 10-fold excess compared with the @entity8200 -positive @entity706 cells in the same inoculum. In vitro, @entity8200 -deficient cells were more sensitive to killing by spleen cells from @entity19 treated with interferon or natural killer-inducing agents. The presence of cold @entity8200 -deficient cells did not activate the killing of @entity8200 -positive cells, and @entity8200 -positive cells did not inhibit killing of @entity8200 -deficient cells. Such mixing experiments revealed a more efficient cold target inhibition by the @entity8200 -deficient cells, although no difference was seen between these and the @entity8200 -positive wild-type cells in target binding assays. When Thy-1.2+, nylon wool adherent or phagocytic populations were removed from normal spleen effectors, the difference in spontaneous cell-mediated cytotoxicity between the @entity8200 -deficient and the @entity8200 -positive cells persisted. This result was also obtained when spleen cell effectors from @entity19 or asialo GM1+ effectors, positively enriched by fluorescence-activated cell sorter, were used. The results show that the selectivity in the rejection of @entity8200 -deficient cells was not determined in the afferent arm alone. The present data fit with a previously proposed model where natural killer cells would bind equally well to both major histocompatibility complex class I negative and class I positive target cells, but only the latter would be able to present a postbinding inhibitory signal allowing them to escape killing which results in outgrowth in vivo and poor cold target competition in vitro.
