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Immune activation in the genital tract may account for increased HIV susceptibility among healthy young women in sub-Saharan Africa
Presented by Craig Cohen (United States).
C. Cohen1, B. Moscicki2, M. Scott2, Y. Ma2, S. Shiboski3, E. Bukusi4, I. Daud4, A. Rebbapragada5, J. Brown6, R. Kaul7
1University of California, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, United States, 2University of California, Pediatrics, San Francisco, United States, 3University of California, Biostatistics and Epidemiology, San Francisco, United States, 4Kenya Medical Research Institute, Centre for Microbiology Research, Nairobi, Kenya, 5University of Toronto, Toronto, Canada, 6University of California, Epidemiology, Los Angeles, United States, 7University of Toronto, Toronto, Canada
Background: The primary target cells for HIV in the genital mucosa are activated CD4+ T-cells while secretory leukocyte protease inhibitor (SLPI) may play a protective role. HIV acquisition rates are very high in young women from many areas of sub-Saharan Africa. We hypothesized that this might relate to genital mucosal immune differences.
Methods: Cervical cytobrushes were collected from 18-24 year old women in San Francisco, CA (n=18) and Kisumu, Kenya (n=36) without genital co-infections during enrollment for a phase 1 trial of VivaGel?. Cryopreserved T-cell and dendritic cell populations were assayed by flow cytometry in a central laboratory. Genital cytokine levels were measured by Luminex and SLPI was assayed by ELISA from fluid collected by cervical vaginal lavage. All participants tested negative for HIV, HSV-2, gonorrhea, chlamydia, trichomonas and bacterial vaginosis, and had abstained from sex for at least seven days prior to enrollment. Wilcoxon rank-sum tests were used to evaluate for differences between sites.
Results: Median [interquartile] genital levels of SLPI were lower in participants from Kisumu compared with San Francisco (Kisumu: 189.9 pg [96.1, 518.8] vs. San Francisco: 474.4 pg [205.7, 816.6]; p < 0.03), and interleukin (IL)-2 levels were higher (Kisumu: 0.48 pg/mg total protein [0.038, 2.3] vs. San Francisco: 0.028 pg/mg total protein [0.038, 0.25]; p < 0.01). Despite a similar number of endocervical CD4+ T-cells in both groups, participants from Kisumu had higher numbers of CD4+ T-cells expressing the early activation marker CD69 with and without the HIV-coreceptor CCR5, as well as activated CD8+ T-cells. Dendritic cell populations were similar in both groups.
Conclusions: Activated mucosal T-cells were increased in the genital tract of young, STI/HIV-free Kenyan women, and SLPI levels were reduced. The causes of these mucosal immune differences are not known, but may partly explain the high HIV incidence in young women from sub-Saharan Africa.
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