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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load
Journal of Immunology, Volume 187, No. 5, Year 2011
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Description
High Ag load in chronic viral infections has been associated with impairment of Ag-specific T cell responses; however, the relationship between Ag load in chronic Mycobacterium tuberculosis infection and functional capacity of M. tuberculosis-specific T cells in humans is not clear. We compared M. tuberculosis-specific T cell-associated cytokine production and proliferative capacity in peripheral blood from adults with progressively higher mycobacterial loads - that is, persons with latent M. tuberculosis infection (LTBI), with smear-negative pulmonary tuberculosis (TB), and smear-positive TB. Patients with smear-positive TB had decreased polyfunctional IFN-γ +IL-2 +TNF-α + and IL-2-producing specific CD4 T cells and increased TNF-α single-positive cells, when compared with smear-negative TB and LTBI. TB patients also had increased frequencies of M. tuberculosis-specific CD8 T cells, compared with LTBI. M. tuberculosis-specific CD4 and CD8 T cell proliferative capacity was profoundly impaired in individuals with smear-positive TB, and correlated positively with ex vivo IFN-γ +IL-2 +TNF-α + CD4 T cells, and inversely with TNF-α single-positive CD4 T cells. During 6 mo of anti-TB treatment, specific IFN-γ +IL-2 +TNF- α + CD4 and CD8 T cells increased, whereas TNF-α and IFN-γ single-positive T cells decreased. These results suggest progressive impairment of M. tuberculosis-specific T cell responses with increasing mycobacterial load and recovery of responses during therapy. Furthermore, these data provide a link between specific cytokine-producing subsets and functional capacity of M. tuberculosis-specific T cells, and between the presence of specific CD8 T cells ex vivo and active TB disease. These data have potentially significant applications for the diagnosis of TB and for the identification of T cell correlates of TB disease progression. Copyright © 2011 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Day, Cheryl Cheryl L.
South Africa, Cape Town
University of Cape Town
United States, Atlanta
Rollins School of Public Health
United States, Atlanta
Emory University
Abrahams, Deborah Ann
South Africa, Cape Town
University of Cape Town
Lerumo, Lesedi
South Africa, Cape Town
University of Cape Town
Van Rensburg, Esme Janse
South Africa, Cape Town
University of Cape Town
Stone, Lynnette
South Africa, Cape Town
University of Cape Town
O'Rie, Terrence
South Africa, Cape Town
University of Cape Town
Pienaar, Bernadette
South Africa, Cape Town
University of Cape Town
de Kock, Marwou
South Africa, Cape Town
University of Cape Town
Kaplan, Gilla
United States, Newark
Public Health Research Institute
Mahomed, Hassan
South Africa, Cape Town
University of Cape Town
Dheda, Keertan U.J.
South Africa, Cape Town
University of Cape Town
Hanekom, Willem Albert
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 331
Authors: 12
Affiliations: 4
Identifiers
Doi:
10.4049/jimmunol.1101122
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Infectious Diseases