Detection of Polyfunctional Mycobacterium tuberculosis–Specific T Cells and Association with Viral Load in HIV‐1–Infected Persons
1HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa; 2Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, Oxford University, Oxford, United Kingdom; 3Partners AIDS Research Center, Massachusetts General Hospital, and 4Division of AIDS, Harvard Medical School, Boston, Massachusetts; and 5Howard Hughes Medical Institute, Chevy Chase, Maryland
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 (
), and the proportion of MTB‐specific IL‐2–secreting CD4 cells was inversely correlated with the HIV‐1 load (
). 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.
Received 24 September 2007; accepted 29 October 2007; electronically published 4 March 2008.
Cited by
Online publication date: 18-Jul-2009.
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Online publication date: 1-Apr-2009.
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Online publication date: 1-Apr-2008.
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(See the editorial commentary by Lalvani and Millington, on pages 941–3.)
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Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grant R01 AI067073); Mark and Lisa Schwartz Foundation.
Presented in part: 3rd South African AIDS Conference, Durban, South Africa, June 2007 (poster A61).
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Present affiliation: South African Tuberculosis Vaccine Initiative, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.