Impact of Estrogen Therapy on Lymphocyte Homeostasis and the Response to Seasonal Influenza Vaccine in Post-Menopausal Women.

It is widely recognized that changes in levels of ovarian steroids modulate severity of autoimmune disease and immune function in young adult women. These observations suggest that the loss of ovarian steroids associated with menopause could affect the age-related decline in immune function, known as immune senescence. Therefore, in this study, we determined the impact of menopause and estrogen therapy (ET) on lymphocyte subset frequency as well as the immune response to seasonal influenza vaccine in three different groups: 1) young adult women (regular menstrual cycles, not on hormonal contraception); 2) post-menopausal (at least 2 years) women who are not receiving any form of hormone therapy (HT) and 3) post-menopausal hysterectomized women receiving ET. Although the numbers of circulating CD4 and CD20 B cells were reduced in the post-menopausal group receiving ET, we also detected a better preservation of naïve B cells, decreased CD4 T cell inflammatory cytokine production, and slightly lower circulating levels of the pro-inflammatory cytokine IL-6. Following vaccination, young adult women generated more robust antibody and T cell responses than both post-menopausal groups. Despite similar vaccine responses between the two post-menopausal groups, we observed a direct correlation between plasma 17β estradiol (E2) levels and fold increase in IgG titers within the ET group. These findings suggest that ET affects immune homeostasis and that higher plasma E2 levels may enhance humoral responses in post-menopausal women

Impact of menopause and ET on IL-6 levels and TNFα and IFNγ production.

<p>(A) Frequency of CD4 and CD8 T cells that secrete TNFα, IFNγ or both in response to CD3 stimulation was determined by intracellular cytokine staining and FCM using PBMC collected during visit 1 before the administration of the influenza vaccine. (B) Plasma IL-6 levels using samples collected during visit 1 were determined by ELISA.</p

Impact of menopause and ET on lymphocyte frequencies.

<p>(A) The number of lymphocytes on visit 1 /μl blood based on complete blood cell counts (CBC) values. (B) Frequency of CD4 T cells, CD8 T cells and CD20 B cells was determined in PBMC using flow cytometry (FCM). The percentages were then converted to absolute numbers of cells/μl blood using the lymphocyte counts obtained from the CBCs. (C) Frequency of naïve (Na), central memory (CM) and effector memory (EM) CD4 T cells was determined using FCM and were then converted to number/μl of blood using the CD4 numbers obtained earlier. (D) Numbers of Na, CM and EM CD8 T cells was determined as described for CD4 T cells. (E) Frequencies of naïve (CD27-) and memory (CD27+) B cells were determined by FCM and then converted to absolute numbers of cells/μl blood using the CD20 numbers obtained earlier.</p