Characterization of Mycobacterium tuberculosis–Specific Cells Using MHC Class II Tetramers Reveals Phenotypic Differences Related to HIV Infection and Tuberculosis Disease
Year: 2017
Type: article
Study design: Observational Study
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.
Source: The Journal of Immunology
Institutions: University of Cape Town, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Ragon Institute of MGH, MIT and Harvard, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Massachusetts Institute of Technology, The Francis Crick Institute, Imperial College London
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Emory University, Wellcome Trust, Francis Crick Institute, Frederick National Laboratory for Cancer Research, European Commission, National Research Foundation, National Institutes of Health, Medical Research Council, National Cancer Institute, National Institute of Allergy and Infectious Diseases, European and Developing Countries Clinical Trials Partnership
Awards: G1145983601, G1288721568, TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development, G2006052962, G2301282499, G2374936369, G2542180245, G2919344005, G3070053804, G3503792436, Host directed therapies against tuberculosis., G386607036, G4115567365, LEVERAGING CESGA TO RESEARCH CENTER OF EXCELLENCE, G434337789, G47196037, G4988656331, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Host directed therapies against tuberculosis., G5888954722, Diversity of CD4+ Th subsets in TB immunity - Impact of HIV infection, G6159686706, G6227691328, Pathogen COinfection:
HIV, Tuberculosis, Malaria and Hepatitis C virus, G6845734885, G7497857799, G7574714948, G790109484, G8116470440, G9000152420
OpenAlex ID: W2744827189