Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs

Estrogen deficiency following ovariectomy or menopause results in bone loss . Although evidence strongly suggests that the immune system is involved in the pathogenesis of estrogen-deficient osteoporosis, it is not clear what role, if any, the T-lymphocyte plays in this process. Therefore, we examine d the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley r ats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surge ry into six groups to receive the following treatments: (A) sham/placebo; ( B) sham/low-dose E-2; (C) sham/high-dose E-2; (D) Ovx/placebo; (E) Ovx/low- dose E-2; (F) Ovx/high-dose E-2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononucle ar cells were isolated from the thymus, peripheral blood, spleen, lymph nod e and bone marrow, and were labeled for flow cytometric analysis using mous e anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigen ic markers. In the thymus, ovariectomy caused a dramatic increase and E-2 t reatment caused a dose-dependent decrease in weight that was proportional t o the number of thymocytes. In the bone marrow, ovariectomy caused a signif icant reduction in the percentage of all T-cell subsets examined and this e ffect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E -2 treatment caused an increase in T-cell subsets in both the sham and Ovx groups, an effect that was more pronounced at d 14 compared with d 28. Alth ough the percentages of some T-cell subsets in the other lymphoid organs/ti ssues were altered by ovariectomy or E-2 treatment at d 0 and 14, all these changes had normalized by d 28 except for CD5 and CD4 cells in peripheral blood. In summary, with the exception of T-lymphocytes in the bone marrow, the effects of varying estrogenic states on T-cells were variable and trans ient. The influence of estrogen status on bone marrow T-lymphocytes suggest s that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional rol e of T-cells in the bone marrow compartment.