Effects of Ovarian Steroids on Immunoglobulin-Secreting Cell Function in Healthy Women

Abstract

To determine the effect of the ovarian hormone cycle on immunity, immunoglobulin-secreting cell (ISC) frequency and lymphocyte subsets were examined in the blood of healthy women. We found that immunoglobulin A (IgA)-secreting cells (IgA-ISC) were fourfold more frequent than IgG-ISC in peripheral blood mononuclear cells (PBMC). Further, the ISC frequency in PBMC was highest (P < 0.05) during the periovulatory stage of the menstrual cycle. Thus, endogenous ovarian steroids regulate the ISC frequency and this may explain why women are more resistant to viral infections and tend to have more immune-mediated diseases than men do.The strength and nature of immune responses differ between women and men. Humoral and cellular immune responses in females are stronger than those in males (2). For example, female mice produce stronger antibody and cell-mediated responses to immunization than males do (9, 34). Immunoglobulin M (IgM), but not IgG, levels and CD4/CD8 T-cell ratios are significantly higher in the blood of women than in that of men (1,19). Women also develop autoimmune diseases at a much higher rate than men do (36). The precise reasons for the observed gender bias in these diseases are unclear; however, it may be related to the generally stronger immune responses of women. These observations clearly demonstrate a role for ovarian steroid hormones in mediation of the immune system.Gender also influences the clinical course of many viral diseases. Females are more likely to develop a Th1-type response after viral exposure, except during pregnancy, when Th2 responses predominate (36). Female mice are more resistant to lethal vesicular stomatitis virus (3, 12), Coxsackie type B-3 virus (22), herpes simplex virus type 1 (4, 6), and Theiler's murine encephalomyelitis virus (18) infections. Further, in viral infections in which Th1 responses are known to produce immune-mediated pathology, such as lymphocytic choriomeningitis virus infections, females have a more severe disease. Clearly, ovarian sex hormones affect the nature and effectiveness of antiviral immunity.We have demonstrated that the menstrual cycle stage has a dramatic effect on IgG and IgA levels in cervicovaginal secretions of macaques that is similar to the changes found in women (21). Further, in rhesus macaques the frequency of immunoglobulin-secreting cells (ISC) and antibody-secreting cells is significantly higher in systemic lymphoid tissues and the vaginal mucosa collected in the periovulatory period of the menstrual cycle than at other stages of menstrual cycle (20). The change in ISC frequency is not due to a change in the relative frequency of lymphocyte subsets, as this does not change during the menstrual cycle (23).In the present study, we sought to confirm that cyclic changes in ovarian steroid hormone levels elicit similar changes in the ISC frequency of women. Thus, we determined the frequency of spontaneous IgG-secreting cells (IgG-ISC) and IgA-ISC in the peripheral blood mononuclear cells (PBMC) of healthy women volunteers throughout th...

Propagation and Dissemination of Infection after Vaginal Transmission of Simian Immunodeficiency Virus

“…This model uses SIV, a primate lentivirus that is closely related to HIV (5) and that can be efficiently transmitted to macaques by vaginal inoculation of cell-free inocula (11,20,21). Further, the rhesus monkey is similar to humans with regard to the populations of target cells (10) and the physiology (4) and immunology (8,9) of the female genital tract.…”

Age and gender specific prevalence of HTLV-1

“…For female donors overall, the older age subgroups had significantly higher HTLV-1 seroprevalence compared with younger subgroups in all pair-wise comparisons (p < 0.0001) except between G [16][17][18][19] and G [20][21][22][23][24][25][26][27][28][29] (Table 1). This trend was also observed for male donors, where G [16][17][18][19] and G 20-29 were not significantly different and all other pair-wise comparisons showed significantly higher seroprevalence for older subgroups (p = 0.0087 between G 20-29 and G 30-39 , and p < 0.0001 for all other pair-wise comparisons, Table 1).…”

“…2,6,[19][20][21] Mother-to-child transmission of HBV and HCV mainly occurs at delivery but rarely via breastfeeding, 22 whereas for HIV, intra-uterine infection and transmission via breast milk are both important. Conflicting reports exist on mother-to-child transmission of HBV and HCV.…”

Sex Differences in Autoimmune Disease from a Pathological Perspective

“…24,101,102 More appropriate animal models for diabetes are urgently needed. Because neutralizing antibody is known to be critical for reducing CVB3 infection in females, 103 males may develop worse viral-induced pancreatic disease.…”