The regulation of the in vitro generation of cytotoxic T lymphocytes (CTLs) directed against hapten-modified syngeneic cells has been investigated. The results indicate that acute intravenous pretreatment with water-soluble hapten, trinitrobenzene sulfonic acid (TNBS), can either positively or negatively affect the in vitro generation of trinitrophenyl (TNP)-specific CTLs. In general, mice bearing the H-2d haplotype are most likely to develop a reduced in vitro response pattern following a single acute in vivo TNBS treatment, wheras mice bearing the H-2k or H-2b haplotypes display either unchanged or augmented in vitro response patterns. We have shown that, in addition to the influences of H-2 genes, non-H-2 genes can also influence the in vitro haptenspecific CTL response following intravenous pretreatment with water-soluble hapten. Further, in two (H-2k X H-2d) F1 combinations between an H-2k strain displaying an unchanged in vitro response pattern following acute in vivo TNBS treatment and an H-2d strain displaying a reduced in vitro response pattern following similar treatment, it was observed that a single in vivo TNBS pretreatment did not induce the unresponsive state when F1,-TNP stimulator cells were used. These results suggest that the mechanisms responsible for the reduced in vitro response pattern are not dominant within the F1 environment. However, when TNP-modified parental stimulators are used, a split-response pattern is observed in cells from TNBS-treated F1, mice which reflect the response patterns of the respective parents. These latter results again emphasize the influence of gene loci on the in vitro response patterns following acute TNBS treatment. In contrast to the significant influence of H-2 and non-H-2 genes on the in vitro TNP-specific response following acute in vivo TNBS treatment, these genes do not appear to significantly influence the in vitro TNP-specific response pattern following chronic TNBS treatment. Chronic TNBS treatment renders all strains tested specifically unresponsive.
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