Lymphocyte immunoregulatory cells present in semen from human immunodeficiency virus (HIV)-infected individuals: A report from the HIV heterosexual transmission study

Abstract

The purpose of this study was to determine the types and distribution of immune subsets present in semen from human immunodeficiency virus (HIV)‐infected (HIV+) individuals and to compare these values with those measures in semen from HIV‐negative (HIV−) individuals. To accomplish this, a direct three‐color monoclonal antibody labeling technique was employed to identify immune cells in fresh ejaculates. Once labeled, the percent of each immune subset present in the ejaculate was determined by flow cytometric analysis. The percent of CD3+ cells present in the semen of the HIV+ group showed no significant difference when compared with semen from the HIV− group. Analysis of the CD4+ subset yielded a significantly lower percent in the HIV+ group than in the HIV− group. The analysis of the CD8+ subset yielded a higher percent of cells present in semen from HIV+ individuals. The CD8 higher value along with lower CD4 value results in a lower CD4/CD8 ratio in the HIV+ group. Further subset studies showed that the percent of cells expressing naive (CD4+CD45RA+) and memory (CD4+CD45RO+) markers was lower in the HIV+ group. This study provides additional data supporting the utility of flow cytometry and monoclonal antibodies to immunophenotypic cells present in semen ejaculates. It is also the first reported application of the technique to a disease‐based model and may be useful to better understand issues of mucosal immunity and transmission of sexually transmitted diseases such as HIV. © 1996 Wiley‐Liss, Inc.

Depletion of CD4+ T Cells in Semen During HIV Infection and Their Restoration Following Antiretroviral Therapy

“…Because CD4 + T cells play an important helper role in both cellular and humoral acquired immune defense functions, the results of these earlier studies suggest that HIV infection has a broad suppressive effect on mucosal immune defense functions at various mucosal sites. A small study performed by Denny and associates 22 showing a 50% reduction in the proportion of CD4 + T cells in semen from HIV + men provided the first evidence that seminal CD4 + T lymphocytes may be depleted following HIV infection. The results of the present study showing decreased concentrations of CD4 + T cells in semen from HIV + men with high peripheral CD4 + cell counts provide evidence that selective CD4 + T cell depletion also occurs in the male genital tract.…”

“…The low numbers of WBC subpopulations in semen preclude routine quantitative analysis by flow cytometry 22. WBCs in semen were enumerated by an immunohistology assay as previously described 30 with slight modifications.…”

“…However, the effects of HIV-infection, disease stage and antiretroviral therapy (ART) on WBC profiles in the male genital tract have not been described. The male genital tract is also populated with memory mucosal T cells 22, 23, and this cell population is targeted by SIV during acute infection in male macaques24. We therefore hypothesize that HIV infection leads to depletion of CD4 + T lymphocytes in the male genital tract.…”

Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

“…209,210 Pudney and Anderson 158 previously reported the expression of the CD4 receptor on lymphocytes and macrophages infiltrating the testis, which represents a potential target for HIV infection. Similar to other mucosal sites, the MRT is populated by mucosal memory T cells, 124,211 which are depleted during acute infection in humans and macaques. 212,213 Semen contains CD4 1 T cells and macrophages, both of which are target cells for HIV infection.…”

“…212,213 Semen contains CD4 1 T cells and macrophages, both of which are target cells for HIV infection. 211,214,215 Interestingly, seminal mucosal CD4 1 T cells were restored following the initiation of anti-retroviral therapy. 213 A recent study showed that primary SIV infection induced a strong inflammatory response, which was associated with increased numbers of leukocytes in primate semen.…”