Cohen CR, Moscicki AB, Scott ME, et al.. Increased levels of immune activation in the genital tract of healthy young women from sub-Saharan Africa

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California 94117, USA.
AIDS (London, England) (Impact Factor: 5.55). 08/2010; 24(13):2069-74. DOI: 10.1097/QAD.0b013e32833c323b
Source: PubMed


To determine whether healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4 T cells) than a similar population in the United States.
A cross-sectional study nested in a phase 1 microbicide trial.
Cervical cytobrushes were collected from 18 to 24-year-old women in San Francisco, California, USA (n = 18) and Kisumu, Kenya (n = 36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, herpes simplex virus 2, gonorrhea, chlamydia, and trichomonas, and had abstained from sex for at least 7 days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. Secretory leukocyte protease inhibitor levels were assayed in cervicovaginal lavage samples. The Wilcoxon rank-sum test was used to compare immune parameters between sites.
The total number of endocervical CD4(+) T cells was slightly higher in participants from San Francisco, but participants from Kisumu had a substantially higher number and proportion of CD4(+) T cells expressing the early activation marker CD69, with and without the HIV coreceptor C-C chemokine receptor type 5, and a greater proportion of activated CD8(+) T cells. Median (interquartile range) genital levels of secretory leukocyte protease inhibitor were lower in participants from Kisumu compared with those from San Francisco [190 (96-519) vs. 474 (206 817) pg/ml, P < 0.03].
Activated mucosal T cells were increased in the genital tract of young, sexually transmitted infection/HIV-free Kenyan women, independent of common genital coinfections, and secretory leukocyte protease inhibitor levels were reduced. The cause of these mucosal immune differences is not known, but could partly explain the high HIV incidence in young women from sub-Saharan Africa.

Download full-text


Available from: Ibrahim I Daud, Jun 24, 2014
  • Source
    • "While the effect of systemic immune activation on HIV susceptibility has not been firmly established, there is evidence that factors other than local inflammation influence the immunologic milieu at mucosal sites of HIV exposure. For example, the genital tracts of Kenyan women have more activated CD4+ T cells compared to women from San Francisco, independent of genital co-infections or behavioral factors that may influence local genital inflammation [13]. In addition, systemic immunological profiles correlate with natural resistance to HIV, as low levels of peripheral T cell activation are found in individuals who remain uninfected despite frequent exposure to HIV [14], [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Among HIV-infected individuals, co-infection with Mycobacterium tuberculosis is associated with faster progression to AIDS. We investigated the hypothesis that M. bovis BCG and M. tuberculosis (Mtb complex) could enhance susceptibility of CD4+ cells to HIV infection. Peripheral blood mononuclear cells (PBMCs) collected from healthy donors were stimulated with M. bovis BCG, M. tuberculosis CDC1551 and M. smegmatis MC(2)155, and stimulated CD4+ cells were infected with R5-and X4-tropic single replication-competent pseudovirus. CD4+ cells stimulated with Mtb complex showed enhanced infection with R5- and X4-tropic HIV, compared to unstimulated cells or cells stimulated with M. smegmatis (p<0.01). Treatment with TLR2 siRNA reversed the increased susceptibility of CD4+ cells with R5- and X4-tropic virus induced by Mtb complex. These findings suggest that TB infection and/or BCG vaccination may be a risk factor for HIV acquisition.
    PLoS ONE 07/2012; 7(7):e41093. DOI:10.1371/journal.pone.0041093 · 3.23 Impact Factor
  • Source
    • "This relatively low frequency of transmission can be explained by a continuum of variables extending from the properties of the infectious inoculum to the properties of the exposed mucosal surfaces. The presence of pre-existing sexually transmitted infections (STI) is widely believed to increase susceptibility to HIV-1 infection for exposed women, presumably by causing damage to mucosal surfaces and signaling the recruitment of inflammatory cell infiltrates [24], [25], [26], [27]. Several previous studies have described interactions between herpes simplex virus (HSV-1 or HSV-2) and HIV-1 [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Normal human premenopausal cervical tissue has been used to derive primary cell populations and to establish ex vivo organ culture systems to study infections with herpes simplex virus (HSV-1 or HSV-2) and human immunodeficiency virus type 1 (HIV-1). Infection with either HSV-1 or HSV-2 rapidly induced multinuclear giant cell formation and widespread damage in mucosal epithelial cells. Subsequent exposure of the damaged mucosal surfaces to HIV-1 revealed frequent co-localization of HSV and HIV-1 antigens. The short-term organ culture system provides direct experimental support for the epidemiological findings that pre-existing sexually transmitted infections, including primary and recurrent herpes virus infections at mucosal surfaces, represent major risk factors for acquisition of primary HIV-1 infection. Epithelial damage in combination with pre-existing inflammation, as described here for overtly normal human premenopausal cervix, creates a highly susceptible environment for the initiation and establishment of primary HIV-1 infection in the sub-mucosa of the cervical transformation zone.
    PLoS ONE 07/2011; 6(7):e22638. DOI:10.1371/journal.pone.0022638 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sexual intercourse is the major means of HIV transmission, yet the impact of semen on HIV infection of CD4(+) T cells remains unclear. To resolve this conundrum, we measured CD4(+) target cell infection with X4 tropic HIV IIIB and HC4 and R5 tropic HIV BaL and SF162 after incubation with centrifuged seminal plasma (SP) from HIV-negative donors and assessed the impact of SP on critical determinants of target cell susceptibility to HIV infection. We found that SP potently protects CD4(+) T cells from infection with X4 and R5 tropic HIV in a dose- and time-dependent manner. SP caused a diminution in CD4(+) T cell surface expression of the HIVR CD4 and enhanced surface expression of the HIV coreceptor CCR5. Consequently, SP protected CD4(+) T cells from infection with R5 tropic HIV less potently than it protected CD4(+) T cells from infection with X4 tropic HIV. SP also reduced CD4(+) T cell activation and proliferation, and the magnitude of SP-mediated suppression of target cell CD4 expression, activation, and proliferation correlated closely with the magnitude of the protection of CD4(+) T cells from infection with HIV. Taken together, these data show that semen protects CD4(+) T cells from HIV infection by restricting critical determinants of CD4(+) target cell susceptibility to HIV infection. Further, semen contributes to the selective transmission of R5 tropic HIV to CD4(+) target cells.
    The Journal of Immunology 11/2010; 185(12):7596-604. DOI:10.4049/jimmunol.1002846 · 4.92 Impact Factor
Show more