Attrition of TCR Vα7.2+ CD161++ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression

Abstract

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8+ T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161++CD8+ T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

Mucosa-Associated Invariant T Cells Are Systemically Depleted in Simian Immunodeficiency Virus-Infected Rhesus Macaques

“…Given multiple previous reports of peripheral blood MAIT cell loss in inflammatory disease models (2,(15)(16)(17)(18)(19)(20), we assessed circulating MAIT cell frequencies in healthy and SIVinfected RMs. Lower frequencies and absolute numbers of MAIT cells were detected in the peripheral blood of SIV-infected versus SIV-uninfected RMs ( Fig.…”

“…ϩ MAIT cells in HIV-infected patients (17,18,20). The migration of MAIT cells to tissue sites of inflammation may therefore be impaired in the context of HIV/SIV infection.…”

“…Indeed, multiple reports have described a loss of circulating MAIT cells in diseases with an inflammatory component, such as obesity and type II diabetes (15), inflammatory bowel disease (16), tuberculosis (2,17), and human immunodeficiency virus (HIV) disease (18)(19)(20). MAIT cells also appear to be highly activated under these conditions and may be recruited to tissue sites of inflammation (15,16,19).…”

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

“…CD8 + CCR6 + mucosal-associated invariant T cells in infected HIV patients tend to have lower surface CCR6 expression compared with healthy control mucosalassociated invariant T cells [56,57], possibly leading to their failure to migrate to key immunological sites.…”

Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8+ T cells in HIV/TB co-infection

“…Multiple evidences support the potential association between CIA and T cell immunosenescence, although it still remains a conundrum as to whether TB plays a critical role in HIV disease progression. We recently showed that HIV/TB co-infection depleted the frequency of mucosal-associated invariant T cells (MAIT) with significant up-regulation of PD-1 [16]. Therefore, the possible role of TB on premature senescence and CIA in HIV disease remains largely elusive.…”