The relationship between exogenous contraceptive hormones and permissiveness of the female

The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed argument. 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations activation phenotype and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA the numbers of CD45 CD3 CD8 CD68 HLA-DR and CCR5 bearing immune cells were significantly (test was used. The test results were interpreted with model showing that progesterone treatment of peripheral blood mononuclear cells (PBMCs) caused a 5- to 10-fold up-regulation of CCR5 in CD14+ monocytes/macrophages.39 Furthermore women in various progesterone-dominant states have been found to have increased expression of cervical and vaginal lymphocytes expressing CCR5.39-41 Interestingly they have also been shown to have G-749 increased susceptibility to acquire HIV-1.42-45 CCR5 is known to be expressed by activated lymphocytes.46 Another marker of lymphocyte activation is the histocompatibility antigen HLA-DR. HLA-DR+ T cells are present in the early phases of HIV-1 contamination47-49 and are thought to account for the majority of the cell populace responsible for dissemination of HIV-1 from your mucosal portal to draining lymph Rabbit Polyclonal to VTI1B. nodes and distant sites.50 Animal models show that HLA-DR+-activated T cells and macrophages are productively infected during the early stage of SIV/HIV contamination and constitute one of the main targets for the computer virus.51 52 In our study DMPA increased CD3+ T cells and HLA-DR+ cells. Our findings are consistent with a large longitudinal study that found that white blood cells (WBCs) and polymorphonuclear monocytes (PMNs) were increased in the cervicovaginal fluid lavage (CVL) of women using hormonal contraception.53 CD3+ cells are widely reported to be the predominant lymphocyte population of the vagina.54-57 Although not as numerous in the cervix and vagina as in the upper reproductive tract vaginal CD3+ T cell populations are not known to be affected by hormonal fluctuations of the menstrual cycle.54 56 The two main subsets of CD3+ T cells are CD4+ and CD8+ cells56 57 however CD8+ T cells can outnumber CD4+ T cells in the vaginal epithelium by as much as 8:1.58 59 CD4+ T cells are a key target for cervicovaginal mucosal HIV-1 infection.32 Other CD4-bearing cells in the lower female genital tract are dendritic cells (DCs) and macrophages.37 and data indicate that intraepithelial and submucosal DCs and CD4+ T lymphocytes and macrophages are the first cells targeted by HIV-1.32 50 60 We detected few vaginal tissue biopsies containing CD4+ cells and the observed cells were confined exclusively to the lamina propria. Of notice in the three tissue samples in which CD4+ cells were detected subclinical inflammation was noted. This is in agreement with previous reports describing limited figures and distribution of CD4+ cells in the vaginal epithelium especially in the absence of infections or other inflammatory conditions.28 34 36 59 64 In this study the presence of STIs or other symptomatic inflammatory vaginal G-749 infections such G-749 as bacterial vaginosis or trichomoniasis was exclusionary. We have found comparable low figures and confined localization of CD4+ cells to the lamina propria in the mucosa of new noninflamed vaginal tissue obtained from patients undergoing anterior and posterior surgical repairs (data not shown). Furthermore parallel positive controls using lymph node tissue displayed strong labeling of CD4+ cells indicating our findings were not due to technical issues in detection (data not shown). The presence of CD4+ cells in a small percentage of biopsies does not rule out their importance in cervicovaginal HIV-1 acquisition given the low incidence of HIV transmission the ability of HIV to penetrate G-749 intact epithelium and the increase in CD4+ cell figures at mucosal sites of inflammation.65 66 Furthermore the average increased susceptibility to HIV-1 reported in observational studies of DMPA users has an approximate mean adjusted HR of 1 1.50 (1.07-2.09).6 14 67 68 Therefore an increase in the number of HIV cell targets even if present only in a small percentage of the users may justify the relatively small increased risk for acquiring the infection seen in the population of DMPA users. In our study although not consistently across all markers certain subjects.