Abstract
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.
Highlights
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Using preset forward- and side-scatter gates, which were based on the identification of splenic lymphocytes, we found that only 10 –20% of the genital tract cells were lymphocytes, and most of these cells labeled with anti-CD3 mAb
We report on a novel population of CD3ϩCD4ϪCD8Ϫ lymphocytes expressing the B cell marker B220
Summary
STD, sexually transmitted disease; IEL, intraepithelial lymphocyte; iIEL, intestinal IEL; uNK, uterine NK; UL, uterine lymphocyte; Tr cell, regulatory T cell; Tg, transgenic; 2-m, 2-microglobulin. The cells that dominate the human uterine mucosa at the time for implantation are uterine NK (uNK) cells These cells express the common leukocyte Ag CD45, as well as CD56, and appear to be under strong hormonal control. We have identified a novel population of small CD3ϩB220low CD4ϪCD8Ϫ T cells in the mouse female genital tract that differs from other known T cell populations in the body. These cells exhibited impaired proliferative responses, but produced cytokine and expressed high levels of CD25 and were strongly down-regulatory on splenic T cell proliferation. The CD3ϩB220lowCD4ϪCD8Ϫ T cells were found in the genital tract of nu/nu, MHC class IIϪ/Ϫ, 2microglobulin (2-m)Ϫ/Ϫ, and CD1Ϫ/Ϫ mice, suggesting that they constitute a unique population of extrathymically derived regulatory T cells (Tr cells)
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