title: Co-infection with Mycobacterium tuberculosis impairs HIV-Specific CD8+ and CD4+ T cell functionality.
abstract: The ability of antigen-specific T cells to simultaneously produce multiple cytokines is thought to correlate with the functional capacity and efficacy of T cells. These 'polyfunctional' T cells have been associated with control of HIV. We aimed to assess the impact of co-infection with Mycobacterium tuberculosis (MTB) on HIV-specific CD8+ and CD4+ T cell function. We assessed T cell functionality in 34 South African adults by investigating the IFN-y, IL-2, TNF-α, IL-21 and IL-17 cytokine secretion capacity, using polychromatic flow cytometry, following HIV Gag-specific stimulation of peripheral blood mononuclear cells. We show that MTB is associated with lower HIV-specific T cell function in co-infected as compared to HIV mono-infected individuals. This decline in function was greatest in co-infection with active Tuberculosis (TB) compared to co-infection with latent MTB (LTBI), suggesting that mycobacterial load may contribute to this loss of function. The described impact of MTB on HIV-specific T cell function may be a mechanism for increased HIV disease progression in co-infected subjects as functionally impaired T cells may be less able to control HIV.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Shivan
authors.initials: S
authors.lastname: Chetty
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Pamla
authors.initials: P
authors.lastname: Govender
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zupkosky
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Mona
authors.initials: M
authors.lastname: Pillay
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.affiliation: Department of Infectious Disease, Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Mahomed-Yunus S
authors.initials: MY
authors.lastname: Moosa
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal, Durban, South Africa; The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America; Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal, Durban, South Africa; The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Victoria O
authors.initials: VO
authors.lastname: Kasprowicz
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060085:Coinfection / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D055985:Latent Tuberculosis / Q000150:complications / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D007376:Interleukin-2; D007378:Interleukins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000098546:Interleukin-21