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.