Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women

Understanding the immune profile of CD4 T cells, the primary targets for HIV, in the female genital tract (FGT) is critical for evaluating and developing effective biomedical HIV prevention strategies in women. However, longitudinal investigation of HIV susceptibility markers expressed by FGT CD4 T...

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Bibliographic Details
Published in:	PloS one 2017-06, Vol.12 (6), p.e0178193-e0178193
Main Authors:	Iyer, Smita S, Sabula, Michael J, Mehta, C Christina, Haddad, Lisa B, Brown, Nakita L, Amara, Rama R, Ofotokun, Igho, Sheth, Anandi N
Format:	Article
Language:	eng
Subjects:	Acquired immune deficiency syndrome Adult Age AIDS Biology and Life Sciences Biopsy Blood CCR5 protein CD27 antigen CD4 antigen CD4-Positive T-Lymphocytes - immunology CD69 antigen Cell adhesion & migration Chemokines Cytometry Design analysis Disease prevention Feasibility Female Female genitalia Flow Flow Cytometry Gene expression Genital tract Genitalia, Female - immunology HIV HIV infection HIV infections HIV Seronegativity Human immunodeficiency virus Humans Immunology Infections Infectious diseases Lymphocytes Lymphocytes T Markers Medicine Medicine and Health Sciences Mucosal immunity Peripheral blood Prevention Profiling Recovery Reproductive organs, Female Research and Analysis Methods Risk Sampling Sampling methods Studies T cells Trauma Vaccines Virology Womens health
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Summary:	Understanding the immune profile of CD4 T cells, the primary targets for HIV, in the female genital tract (FGT) is critical for evaluating and developing effective biomedical HIV prevention strategies in women. However, longitudinal investigation of HIV susceptibility markers expressed by FGT CD4 T cells has been hindered by low cellular yield and risk of sampling-associated trauma. We investigated three minimally invasive FGT sampling methods to characterize and compare CD4 T cell yield and phenotype with the goal of establishing feasible sampling strategies for immune profiling of mucosal CD4 T cells. FGT samples were collected bimonthly from 12 healthy HIV negative women of reproductive age in the following order: 1) Cervicovaginal lavage (CVL), 2) two sequential endocervical flocked swabs (FS), and 3) two sequential endocervical cytobrushes (CB1, CB2). Cells were isolated and phentoyped via flow cytometry. CD4 T cell recovery was highest from each individual CB compared to either CVL or FS (p < 0.0001). The majority of CD4 T cells within the FGT, regardless of sampling method, expressed CCR5 relative to peripheral blood (p < 0.01). Within the CB, CCR5+ CD4 T cells expressed significantly higher levels of α4β7, CD69, and low levels of CD27 relative to CCR5- CD4 T cells (all p < 0.001). We also identified CD4 Treg lineage cells expressing CCR5 among CB samples. Using three different mucosal sampling methods collected longitudinally we demonstrate that CD4 T cells within the FGT express CCR5 and α4β7 and are highly activated, attributes which could act in concert to facilitate HIV acquisition. FS and CB sampling methods can allow for investigation of strategies to reduce HIV target cells in the FGT and could inform the design and interpretation microbicide and vaccine studies in women.
ISSN:	1932-6203 1932-6203