A unique population of extrathymically derived alpha beta TCR+CD4-CD8- T cells with regulatory functions dominates the mouse female genital tract.
A better understanding of the regulatory role of genital tract T cells is much needed. In this study, we have analyzed the phenotype, distribution, and function of T lymphocytes in the female genital tract of naive, pregnant, or Chlamydia trachomatis-infected C57BL/6 mice. Unexpectedly, we found that the dominant lymphocyte population (70-90%) in the genital tract was that of CD3(+)alphabetaTCR(int)CD4(-)CD8(-) T cells. Moreover, these cells were CD90(low) but negative for the classical T cell markers CD2 and CD5. The CD3(+)B220(low) cells were NK1.1 negative and found in nude mice as well as in mice deficient for MHC class II, beta(2)-microglobulin, and CD1, indicating extrathymic origin. They dominated the KJ126(+)Vbeta8.2(+) population in the genital tract of DO11.10 OVA TCR-transgenic mice, further supporting the idea that the CD3(+)B220(low) cells are truly T cells. The function of these T cells appeared not to be associated with immune protection, because only CD4(+) and CD8(+) T cells increased in the genital tract following chlamydial infection. Notwithstanding this, the infected, as well as the uninfected and the pregnant, uterus was dominated by a high level of the CD3(+)CD4(-)CD8(-)B220(low) cells. Following in vitro Ag or polyclonal stimulation of the CD3(+)CD4(-)CD8(-)B220(low) cells, poor proliferative responses were observed. However, these cells strongly impaired splenic T cell proliferation in a cell density-dependent manner. A large fraction of the cells expressed CD25 and produced IFN-gamma upon anti-CD3 plus anti-CD28 stimulation, arguing for a strong regulatory role of this novel T cell population in the mouse female genital tract.
Johansson
Martina
M
Department of Clinical Immunology, University of Göteborg, S-413 46 Göteborg, Sweden. tina.johansson@microbio.gu.se
Lycke
Nils
N
D000818:Animals; D000918:Antibody Specificity; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology; D002999:Clone Cells; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014591:Uterine Diseases / Q000276:immunology; D014599:Uterus / Q000737:chemistry / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D007130:Immunoglobulin Idiotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens