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J Immunol. 2017 Aug 9. pii: ji1700849. doi: 10.4049/jimmunol.1700849. [Epub ahead of print]

Characterization of Mycobacterium tuberculosis-Specific Cells Using MHC Class II Tetramers Reveals Phenotypic Differences Related to HIV Infection and Tuberculosis Disease.

Author information

1
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, 7925 Cape Town, South Africa.
2
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
3
Wellcome Center for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
4
Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701.
5
Ragon Institute of MGH, MIT and Harvard, Boston, MA 02139.
6
Department of Medicine, Imperial College London, W2 1PG London, United Kingdom; and.
7
The Francis Crick Institute, NW1 2AT London, United Kingdom.
8
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, 7925 Cape Town, South Africa; cr.riou@uct.ac.za.

Abstract

A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4+ T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4+ T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M.tuberculosis-specific MHC class II tetramers. We examined the phenotype as well as function of ex vivo M. tuberculosis-specific tetramer+CD4+ T cells using flow cytometry. The numbers of M. tuberculosis-specific tetramer+CD4+ T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. However, although HIV-uninfected persons with latent TB infection exhibited ex vivo M. tuberculosis-specific CD4+ T cells predominantly of a CXCR3+CCR6+CCR4- (Th1*) phenotype, aTB or HIV infection was associated with a contraction of this subset. Nevertheless, in individuals with aTB and/or HIV infection, circulating ex vivo M. tuberculosis-specific CD4+ T cells did not display defects in exhaustion or polyfunctionality compared with healthy HIV-uninfected individuals with latent TB infection. Collectively, these data suggest that increased susceptibility to TB disease could be related to a loss of circulating Th1* CD4+ T cells rather than major changes in the number or function of circulating CD4+ T cells.

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