Fas ligand in the uterus of the non-pregnant mouse induces apoptosis of CD4+ T cells.
The role of FasL in the reproductive tissues of the non-pregnant mouse may be the induction of apoptosis of activated T cells for the prevention of unwanted inflammatory responses secondary to infection. This study was undertaken to identify cell and tissue types that typically express FasL in the uterus and oviduct of the mouse and to establish whether FasL on the surface of these cells was able to induce T cell apoptosis. FasL in the mouse uterus and oviduct was demonstrated using three independent methods: RT-PCR, Western blot and immunocytochemistry. The protein was present in the epithelial and mesenchymal cells of the uterus and showed a granular pattern in the apical epithelial portion. Although this suggests the presence of vesicles, surface expression was also detected by flow cytometry of isolated uterine cells. Exogenous administration of estradiol and progesterone had no significant effect on the expression and localization of FasL. The ability of uterine cells to induce FasL-dependent apoptosis of activated CD4+T cells was examined by incubation of phytohemagglutinin-treated T cells with cultured uterine cells. TUNEL and flow cytometric analyses showed that CD4+T cells experienced apoptosis after 5h of co-incubation. Neutralizing antibodies inhibited apoptosis demonstrating that a biologically active FasL is present in the reproductive tissues of the mouse. Results indicate that FasL is a biologically active molecule present in epithelial and mesenchymal cells of the uterus and the oviduct of the non-pregnant mouse that might restrain local immune response by induction of apoptosis of CD4+T lymphocytes.
Imarai
Mónica
M
Laboratorio de Immunología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Correo 40, Casilla 33, Santiago, Chile. cimarai@usach.cl
Varela-Nallar
Lorena
L
Figueroa-Gaete
Claudio
C
González
Patricia
P
Valdés
Daniel
D
Velásquez
Luis
L
Cárdenas
Hugo
H
Maisey
Kevin
K
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004958:Estradiol / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol