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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Optimizing viable leukocyte sampling from the female genital tract for clinical trials: An international multi-site study
PLoS ONE, Volume 9, No. 1, Article e85675, Year 2014
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Description
Background: Functional analysis of mononuclear leukocytes in the female genital mucosa is essential for understanding the immunologic effects of HIV vaccines and microbicides at the site of HIV exposure. However, the best female genital tract sampling technique is unclear. Methods and Findings: We enrolled women from four sites in Africa and the US to compare three genital leukocyte sampling methods: cervicovaginal lavages (CVL), endocervical cytobrushes, and ectocervical biopsies. Absolute yields of mononuclear leukocyte subpopulations were determined by flow cytometric bead-based cell counting. Of the non-invasive sampling types, two combined sequential cytobrushes yielded significantly more viable mononuclear leukocytes than a CVL (p<0.0001). In a subsequent comparison, two cytobrushes yielded as many leukocytes (∼10,000) as one biopsy, with macrophages/monocytes being more prominent in cytobrushes and T lymphocytes in biopsies. Sample yields were consistent between sites. In a subgroup analysis, we observed significant reproducibility between replicate same-day biopsies (r = 0.89, p = 0.0123). Visible red blood cells in cytobrushes increased leukocyte yields more than three-fold (p = 0.0078), but did not change their subpopulation profile, indicating that these leukocytes were still largely derived from the mucosa and not peripheral blood. We also confirmed that many CD4+ T cells in the female genital tract express the α4β7 integrin, an HIV envelope-binding mucosal homing receptor. Conclusions: CVL sampling recovered the lowest number of viable mononuclear leukocytes. Two cervical cytobrushes yielded comparable total numbers of viable leukocytes to one biopsy, but cytobrushes and biopsies were biased toward macrophages and T lymphocytes, respectively. Our study also established the feasibility of obtaining consistent flow cytometric analyses of isolated genital cells from four study sites in the US and Africa. These data represent an important step towards implementing mucosal cell sampling in international clinical trials of HIV prevention. © 2014 McKinnon et al.
Authors & Co-Authors
McKinnon, Lyle R.
Canada, Toronto
University of Toronto
Kenya, Nairobi
University of Nairobi
Hughes, Sean M.
United States, Seattle
University of Washington
De-Rosa, Stephen C.
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Martinson, Jeffrey A.
United States, Chicago
Rush University Medical Center
Plants, Jill
United States, Chicago
Rush University Medical Center
Brady, Kirsten E.
United States, Chicago
Rush University Medical Center
Gumbi, Pamela P.
South Africa, Cape Town
University of Cape Town
Adams, Devin J.
United States, Seattle
Fred Hutchinson Cancer Research Center
Vojtech, Lucia N.
United States, Seattle
University of Washington
Galloway, Christine G.
United States, Seattle
Fred Hutchinson Cancer Research Center
Fialkow, Michael
United States, Seattle
University of Washington
Lentz, Gretchen
United States, Seattle
University of Washington
Gao, Dayong
United States, Seattle
University of Washington
Shu, Zhiquan
United States, Seattle
University of Washington
Nyanga, Billy
Kenya, Nairobi
University of Nairobi
Izulla, Preston
Kenya, Nairobi
University of Nairobi
Kimani, Joshua
Kenya, Nairobi
University of Nairobi
Kimwaki, S.
Kenya, Nairobi
University of Nairobi
Bere, Alfred
South Africa, Cape Town
University of Cape Town
Moodie, Zoe
United States, Seattle
Fred Hutchinson Cancer Research Center
Landay, Alan L.
United States, Chicago
Rush University Medical Center
Passmore, Jo Ann Shelley
South Africa, Cape Town
University of Cape Town
South Africa, Johannesburg
National Health Laboratory Service
Kaul, Rupert
Canada, Toronto
University of Toronto
Kenya, Nairobi
University of Nairobi
Canada, Toronto
University Health Network University of Toronto
Novak, Richard M.
United States, Chicago
University of Illinois College of Medicine
McElrath, Margaret Juliana
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Hladik, Florian
United States, Seattle
University of Washington
United States, Seattle
Fred Hutchinson Cancer Research Center
Statistics
Citations: 49
Authors: 26
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pone.0085675
e-ISSN:
19326203
Research Areas
Infectious Diseases
Sexual And Reproductive Health
Participants Gender
Female