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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons
Journal of Infectious Diseases, Volume 197, No. 7, Year 2008
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Description
Background. The human immunodeficiency virus type 1 (HIV-1) epidemic is associated with a significant increase in the incidence of tuberculosis (TB); however, little is known about the quality of Mycobacterium tuberculosis (MTB)-specific cellular immune responses in coinfected individuals. Methods. A total of 137 HIV-1-positive individuals in Durban, South Africa, were screened with the use of overlapping peptides spanning Ag85A, culture filtrate protein 10 (CFP-10), early secretory antigen target 6 (ESAT-6), and TB10.4, in an interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay. Intracellular cytokine staining for MTB-specific production of IFN-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2 was performed, as was ex vivo phenotyping of memory markers on MTB-specific T cells. Results. A total of 41% of subjects responded to ESAT-6 and/or CFP-10, indicating the presence of latent MTB infection. The proportion of MTB-specific IFN-γ+/TNF- α+ CD4+ cells was significantly higher than the proportion of IFN-γ+/IL-2+ CD4+ cells (P = .0220), and the proportion of MTB-specific IL-2-secreting CD4 cells was inversely correlated with the HIV-1 load (P = .0098). MTB-specific CD8 T cells were predominately IFN-γ+/TNF-α+/IL-2 -. Ex vivo memory phenotyping of MTB-specific CD4 and CD8 T cells indicated an early to intermediate differentiated phenotype for the population of effector memory cells. Conclusions. Polyfunctional MTB-specific CD4 and CD8 T cell responses are maintained in the peripheral blood of HIV-1-positive individuals, in the absence of active disease, and the functional capacity of these responses is affected by HIV-1 disease status. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Day, Cheryl Cheryl L.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Mkhwanazi, Nompumelelo Prudence
South Africa, Durban
University of Kwazulu-natal
Reddy, Sharon
South Africa, Durban
University of Kwazulu-natal
Mncube, Zenele
South Africa, Durban
University of Kwazulu-natal
van der Stok, Mary
South Africa, Durban
University of Kwazulu-natal
Klenerman, Paul
United Kingdom, Oxford
Nuffield Department of Medicine
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United Kingdom, Oxford
Nuffield Department of Medicine
United States, Boston
Harvard Medical School
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 123
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1086/529048
ISSN:
00221899
Research Areas
Cancer
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Study Locations
South Africa