Impact of androgen therapy in Sjögren's syndrome: hormonal influence on lymphocyte populations and Ia expression in lacrimal glands of MRL/Mp-lpr/lpr mice.
Recent research has demonstrated that androgen treatment dramatically curtails lymphocyte infiltration in the lacrimal glands of a mouse model of Sjögren's syndrome. The purpose of the current study was to determine whether this androgen action involves the selective suppression of specific lymphocyte populations or Ia expression in lacrimal tissue. Autoimmune female MRL/Mp-lpr/lpr mice were administered placebo- or testosterone-containing compounds for 0, 17, or 34 d. Then lacrimal glands were obtained and processed for immunohistochemical evaluation. Results demonstrated that in pretreatment mice, lacrimal lymphoid foci were composed predominantly of Thy 1.2+ cells, bearing L3T4 (helper T cell) or B220 surface antigens. In contrast, suppressor T cells (Lyt 2+) and surface IgM-bearing B cells represented minority populations in the immune infiltrates. Class II antigen (Ia) expression was observed on over 40% of the infiltrate lymphocytes and occasionally on epithelial cells close to the lymphoid focus. During the experimental time course, the extent of lymphocyte infiltration increased in glands of placebo-treated mice. This cellular accumulation was associated with an elevation in the frequency of B220+ cells, but not that of other lymphocyte subclasses. Testosterone administration induced a striking diminution in the area encompassed by all immune cell populations. Moreover, hormone therapy significantly reduced the frequency of B220+ cells in focal infiltrates. Overall, these findings demonstrate that androgen exposure stimulates a decrease in the quantity, but not necessarily the entire lymphocyte composition, of lymphoid aggregates in lacrimal glands of MRL/lpr mice.
Sato
E H
EH
Department of Ophthalmology, Harvard Medical School, Eye Research Institute, Boston, Massachusetts 02114.
Ariga
H
H
Sullivan
D A
DA
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010919:Placebos; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013739:Testosterone / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003692:Delayed-Action Preparations; D000949:Histocompatibility Antigens Class II; D010919:Placebos; D013739:Testosterone