Evidence for a unique expression of CD4 on murine vaginal CD4⁺ cells

Abstract

SUMMARY Mucosal cell-mediated immunity (CMI) by CD4+ T cells is postulated to be important for host defence against several vaginal pathogens. In addition to the recognized phenotypic distinctions of resident vaginal T lymphocytes, we recently provided evidence by¯uorescence-activated cell sorter (FACS) that murine vaginal CD4 + T lymphocytes, are differentially recognized by two epitopedistinct anti-CD4 antibodies, suggesting that the CD4 protein on vaginal CD4+ cells is atypically expressed. In the present study, we con®rm this by FACS and immunohistochemistry under nondenaturing conditions using two additional anti-CD4 antibodies. However, positive immunohistochemical staining of vaginal CD4+ cells under denaturing conditions revealed that the CD4 epitope in question is indeed present within the CD4 protein. Using reverse transcription polymerase chain reaction, ampli®cation of CD3, T-cell receptor-b (TCR-b), and TCR-d mRNA from lymph node and vaginal tissue, and CD4 mRNA from lymph node tissue was demonstrable. In contrast, ampli®cation of CD4 mRNA from vaginal tissue, vaginal enriched lymphoid cells, or a puri®ed (FACS-sorted) population of vaginal-speci®c CD4 + cells using two distinct primer sets was not demonstrable. Altogether, our results provide evidence that the CD4 protein on vaginal CD4 + T cells is conformationally distinct compared with its systemic counterpart, either as a result of a unique CD4 mRNA sequence or from a stable interaction of soluble CD4 with the surface of vaginal T cells.

Chlamydia trachomatis Infection Does Not Enhance Local Cellular Immunity against Concurrent Candida Vaginal Infection

“…Thus, using GK1.5 anti-CD4 antibodies, CD4 ϩ cells will be detected in the vagina only if they have infiltrated from the systemic compartment. The lack of detectable CD4 ϩ cells in Candida-infected mice in this study is consistent with those previous observations (18). In fact, based on the lack of a more enhanced protection against Candida in dually infected mice, one would predict that the infiltrating T cells were Chlamydia specific and not Candida specific, although formal confirmation will require in vitro antigen-specific blastogenesis of genital tract T cells.…”

“…However, no increases in CD4 ϩ cells were noted in mice that received a challenge Candida infection alone. Previously, Wormley et al (18) found in the vaginas of naive mice a phenotypically distinct population of CD4 cells that was not detected with the commonly used anti-CD4 monoclonal antibody against the GK1.5 epitope. Thus, using GK1.5 anti-CD4 antibodies, CD4 ϩ cells will be detected in the vagina only if they have infiltrated from the systemic compartment.…”

Estrogen treatment induces a novel population of regulatory cells, which suppresses experimental autoimmune encephalomyelitis

“…In the past few years, researchers have discovered several new populations of regulatory T cells with previously unknown phenotypes, including those found in the murine vaginal tissue (Wormley et al, 2000) and female genital tracts (Johansson and Lycke, 2003). Classical regulatory CD4 ϩ CD25 ϩ T cells have been shown to inhibit several autoimmune diseases (Mason and Powrie, 1998;Roncarolo and Levings, 2000;Maloy and Powrie, 2001), including EAE (Kohm et al, 2002), and to control type 1 diabetes in rats and mice (Green et al, 2002).…”

A Unique Population of Extrathymically Derived αβTCR+CD4−CD8− T Cells with Regulatory Functions Dominates the Mouse Female Genital Tract

“…B220 ϩ CD19 Ϫ cells have previously been noted in the murine female genital tract (37) but not further investigated. Moreover, a phenotypically unusual T cell population in the vaginal tissue was described by Wormley et al (38), using a special mAb identifying an atypical form of CD4 (11). The CD4 ϩ cells in the vagina were detected using 2B6 but not GK1.5, two epitopedistinct anti-CD4 Abs that are both recognized by splenic CD4 ϩ T cells.…”