In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more resistant to certain infections, and suffer a higher incidence of autoimmune diseases. Disease expression is also affected by the reproductive status of the female. As sex steroids-estrogens, progesterone and testosterone-differ between gender and within different reproductive stages, a lot of research has focussed on the effects of sex hormones on immune responses. Although there is also a vast literature on the effects of sex hormones on immune responses in animals, in this review we will focus on the most intriguing effects and mechanisms by which sex hormones affect different components of the immune system in humans.

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Sex hormones and the immune response in humans

The effects of hormones on sex differences in infection: from genes to behavior.

Effects of gender and sex steroids on the immune response

Women mount more vigorous antibody- and cell-mediated immune responses following either infection or vaccination than men. The incidence of most autoimmune diseases is also higher in women than in men; however, during pregnancy many autoimmune diseases go into remission, only to flare again in the early post-partum period. Successful pregnancy requires that the female immune system tolerate the presence of a semi-allogeneic graft for 9 months. Oral contraceptive use can increase susceptibility to certain genital tract infections and sexually transmitted diseases in women. Moreover, treatment of mice and rats with female sex hormones is required to establish animal models of genital tract Chlamydia, Neisseria and Mycoplasma infection. This review describes what is currently known about the effects of the female sex hormones oestradiol and progesterone on innate and adaptive immune responses in order to provide a framework for understanding these sex differences. Data from both human and animal studies will be reviewed.

Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone.

https://www.cell.com/parasitology/pdf/0169-4758(88)90077-4.pdf

Sex hormones and the course of parasitic infection

The immune response has been reported to be modulated by sex hormones in several models, and estrogen receptors have been demonstrated in the human thymus. We therefore investigated the presence of estrogen and androgen receptors among human peripheral T cells; thoracic duct lymph provided large amounts of circulating lymphocytes. Pure T cells were obtained by negative selection by using complement-dependent cytotoxicity with a monoclonal antibody against a monomorphic determinant of class II histocompatibility antigen (HLA-DR). Furthermore, subsets of OKT8-positive and OKT8-negative lymphocytes were selected by using an OKT8-like monoclonal antibody. Sex steroid binding was determined on purified nuclei; no androgen receptors could be demonstrated on peripheral T cells. The cytoplasmic [3H] 17-beta-estradiol-receptor complex was always translocated to the nucleus in vitro within 1 hr at 37 degrees C; no estrogen receptors were demonstrable on purified OKT4-positive subsets. Assuming that estrogen receptors were evenly distributed among OKT8-positive cells, their level could be estimated to be about 40 fmol/mg DNA. The restriction of estrogen receptors to T cells bearing the "suppressor-cytotoxic" phenotype suggests a possible pathway for the modulation of T cell suppressive activities by estrogens.

S. Saez

Papers

Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells.