Androgen regulation of intra-and extra-thymic T cells and its effect on sex differences in the immune system

Male predominance of malignant disease and female predominance of autoimmune diseases is widely known in humans. To elucidate one of the underlying mechanisms, we examined whether sex differences exist at the level of extra-thymic T cells in various organs of mice under physiological conditions. Effects of castration and testosterone administration were also examined. Intra- and extra-thymic T cells with T cell receptors (TCR) of bright and intermediate intensities, respectively, and with nil and high levels of the interleukin-2 receptor beta-chain respectively, were identified by immunofluorescence. Of the three strains tested, it was demonstrated that intermediate TCR cells were predominant in the liver of female mice. In the liver of male mice after bilateral orchidectomy, mononuclear cells increased and intermediate TCR cells predominated as if they were female; testosterone treatment prevented this immunological consequence of orchidectomy. As extra-thymic T cells comprise a considerable proportion of self-reactive forbidden clones and possess cytotoxic activity against syngeneic tumour cells, the present results suggest a possible relationship between (a) physiologically low levels of extra-thymic T cells in males and the male predominance of malignancy, and (b) the high levels of extra-thymic T cells in females and female predominance of autoimmune diseases.