title: Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs.
abstract: 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 examined the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley rats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surgery into six groups to receive the following treatments: (A) sham/placebo; (B) sham/low-dose E2; (C) sham/high-dose E2; (D) Ovx/placebo; (E) Ovx/low-dose E2; (F) Ovx/high-dose E2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononuclear cells were isolated from the thymus, peripheral blood, spleen, lymph node and bone marrow, and were labeled for flow cytometric analysis using mouse anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigenic markers. In the thymus, ovariectomy caused a dramatic increase and E2 treatment caused a dose-dependent decrease in weight that was proportional to the number of thymocytes. In the bone marrow, ovariectomy caused a significant reduction in the percentage of all T-cell subsets examined and this effect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E2 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. Although the percentages of some T-cell subsets in the other lymphoid organs/tissues were altered by ovariectomy or E2 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 transient. The influence of estrogen status on bone marrow T-lymphocytes suggests that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional role of T-cells in the bone marrow compartment.
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: F F
authors.initials: FF
authors.lastname: Safadi
authors.forename: I R
authors.initials: IR
authors.lastname: Dissanayake
authors.forename: G G
authors.initials: GG
authors.lastname: Goodman
authors.forename: R A
authors.initials: RA
authors.lastname: Jago
authors.forename: A E
authors.initials: AE
authors.lastname: Baker
authors.forename: A R
authors.initials: AR
authors.lastname: Bowman
authors.forename: D A
authors.initials: DA
authors.lastname: Sass
authors.forename: S N
authors.initials: SN
authors.lastname: Popoff
authors.forename: S
authors.initials: S
authors.lastname: Epstein
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000032:analysis; D018956:CD5 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002469:Cell Separation; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000172:deficiency* / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000166:cytology*; D010052:Ovariectomy; D010919:Placebos; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D004967:Estrogens; D010919:Placebos; D004958:Estradiol