Sex-dependent local cellular immunity to alloantigens

A local component of cellular immunity was detected in mice that had been immunized against histocompatibility antigens. The status of this local immunity was determined using a node-onto-kidney (NOK) assay in which lymph nodes draining the site of immunization as well as distant (nondraining) lymph nodes of the immunized mice were grafted onto the kidneys of mice of the immunizing strain. In this assay, the weight gained by each node piece was taken as a measure of its immunological responsiveness. The responsiveness of a draining lymph node was directly compared with that of a distant node after both had been grafted onto the same host kidney. We consistently found that the draining lymph nodes of immunized male mice were more responsive than their distant nodes, whereas the draining lymph nodes of immunized female mice were less responsive than their distant nodes. Male mice were converted to the female pattern of hyporesponsiveness in the draining nodes by performing bilateral orchidectomy, suggesting that the male pattern depends upon the presence of testicular hormones. Additional studies showed there was a significant reduction in the reactivity of uterine draining lymph nodes during both syngeneic and allogeneic pregnancy, raising the possibility that the female pattern of hyporesponsiveness facilitates fetal survival by reducing the maternal immune response to fetal antigens and alloantigens during pregnancy.