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After infection with LP-BM5 murine leukemia viruses, susceptible strains of mice develop a severe and progressive immunodeficiency disease, termed murine AIDS (MAIDS), features of which include markedly impaired T cell response to mitogens or specific Ag stimulation and decreased production of IL-2. Since an elevation of intracellular calcium concentration resulting from binding of Ag to the TCR is associated with IL-2 production, T cells from mice either uninfected or infected with LP-BM5 murine leukemia viruses were examined by a calcium mobilization assay. Both CD4+ and CD8+ T cells from infected mice manifested impaired calcium mobilization responses upon in vitro stimulation with anti-CD3 mAb or Con A. The abnormalities appeared early after virus inoculation and showed no difference in time course between subsets of T cells. Frequencies of prestimulation calcium-positive cells among both CD4+ and CD8+ cells in mice with MAIDS were significantly higher than those for uninfected mice. These abnormalities were associated with presence of the MAIDS-inducing defective virus genome, but were not induced by infection of mice genetically resistant to development of MAIDS or with nonpathogenic helper murine leukemia virus, a virus component that induces high spontaneous proliferation of T cells, even in MAIDS-resistant mice.

Mice administered morphine as a s.c. pellet implant exhibit a marked and sustained thymic hypoplasia as well as suppression of T lymphocyte functions. In the present study, the effects of morphine on thymocyte differentiation were characterized. Morphine produced a significant decrease in both the number and proportion of CD4+/CD8+ double positive (DP) cells. The percentage of the CD4+/CD8-, CD4-/CD8+, and CD4-/CD8- double negative subsets in these mice was proportionally increased. Morphine also increased the proportion of cells expressing either the epsilon-chain of the CD3 complex or the IL-2R. The initial reduction in the proportion of DP thymocytes appeared fully recovered by 10 days post-implantation, although the number of DP thymocytes gradually returned to normal over a 3-wk period. Morphine administration resulted in a marked increase in serum corticosterone levels, and a single injection of dexamethasone mimicked the effects of morphine on thymus differentiation. Furthermore, adrenalectomy abolished the morphine-induced decrease in CD4+/CD8+ thymocytes relative to a sham-operated group. The present findings are consistent with the hypothesis that morphine-induced thymic hypoplasia may be mediated by an increase in the circulating levels of corticosterone.

Murine cytotoxic responses to TNP-modified syngeneic cells (TNP-self) have been shown to exhibit preferential recognition of K or D end self products encoded by the H-2 complex. In the present study, a number of B10 congenic and recombinant mouse strains were investigated to determine the H-2K and H-2D-restricted FTC-self CTL response patterns, and these were compared with the CTL response patterns obtained for TNP-self. The results indicate that for strains possessing the H-2k,d,h2,h4 haplotypes, respectively, preferential CTL responses were observed against FTC recognized in association with Kk over Dk, Dd over Kd, and Kk over Db. These patterns of preferential CTL responses were the same as those reported for TNP-self as well as several anti-viral CTL responses. In contrast to the results obtained in the B10.A strain, in which Kk preference was observed over Dd for TNP-self CTL, no preferential CTL response was observed when FTC was recognized in association with Kk and with Dd. In this context, it was observed that the CTL response to FTC recognized in association with Dd was particularly strong. This strong D end-associated response was shown to involve D locus products, and no evidence was obtained indicating that L locus self products were involved. These studies are discussed with respect to the possibility that different haptens can be recognized by CTL in association with different self determinants encoded by the same H-2 gene products.

Spleen cells from mouse strains expressing the H-2b haplotype (C57BL/6J, C57BL/6N, C57BL/10J, and C3H.SW) were compared for their ability to generate primary in vitro cytotoxic responses to autologous cells modified with either fluorescein isothiocyanate (FITC) (FTC-self) or trinitrobenzene sulfonate (TNBS) (TNP-self). The resulting hapten-specific cytotoxic T lymphocyte (CTL) responses were assayed on hapten-self Con A blast target cells. Among the four H-2b strains tested, C57BL/6J and C57BL/6N were high responders, whereas C57BL/10J and C3H.SW were low responders for CTL generated against FTC-self. Studies using (C57BL/6J x C3H.SW)F1 responding cells and F1 or parenteral-modified stimulating cells indicated that the F1 cells generated cytotoxic activity equivalent to that of the high-responder strain C57BL/6J. Further comparisons of the C57BL/6J and C2H.SW strains indicated that C57BL/6J is a high responder to both FTC-self and TNP-self, whereas C3H.SW is a high responder to TNP-self but a low responder to FTC-self. The results of this study indicate that non-H-2-linked genetic control of CTL response to hapten-self depends not only on the self determinant but also on the foreign antigens.