Genetic studies in NZB mice. IV. The effect of sex hormones on the spontaneous production of anti-T cell autoantibodies.

Hybrid NZB X NZW or NZB X DBA/2 females have markedly accelerated development of autoimmunity when compared with their respective male littermates. This difference is attributable to the ability of male sex hormones to retard the expression of autoimmunity. In contrast to the sex differences in expression of autoimmunity in F1 mice, parental NZB males and females have only minor differences in disease expression. We have been investigating the basis for the difference in anti-T cell antibody production between NZB and F1 mice. In this study, the appearance of antibodies cytotoxic for T cells (NTA) was studied in NZB and DBA/2 mice and in their F1 hybrids and backcross progeny. A major sex difference in NTA production was observed in the F1 hybrids; females produced more NTA than did males. Castration of males led to a marked increase in NTA production. Furthermore, the NTA production of castrated male and female F1 mice was significantly suppressed by administration of testosterone in Silastic capsules. In contrast to the studies in F1 mice, we found little difference between intact male and female parental NZB mice at any age studied. Furthermore, NZB mice of both sexes who were given androgen-containing capsules at 2 weeks of age failed to demonstrate a decrease in NTA production. This result suggested an androgen insensitivity in NZB mice with regard to NTA production. This insensitivity, which appears to be a recessive trait, may help to explain why NZB mice do not manifest the sex differences in disease expression observed in the F1 hybrids.