Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression.

Alireza Saeidi,Hong Y Tan,Sasheela Ponnampalavanar,Muttiah Barathan,Esaki M Shankar,Marie Larsson,Vijayakumar Velu,Devi V Rukumani,Adeeba Kamarulzaman,Yean K Yong,Rami Al-Batran,Abdul W Ansari,Haider A Al-Darraji,Vicky L Tien Tien

doi:10.1371/journal.pone.0124659

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.

Highlights

Human immunodeficiency virus type 1 (HIV-1) infection leads to dramatic loss of CD4+ T cells and increased systemic T-cell activation contributing to increased susceptibility to opportunistic infections (OIs), especially with Mycobacterium tuberculosis (MTB) [1,2,3]
We found that the number of Mucosal-associated invariant T (MAIT) cells was severely depleted in both HIV mono- and HIV/TB co-infected patients whereas the number of CD161+CD8+ T cells was stably maintained in patients
It has been suggested that depletion of MAIT cells could result from redistribution to other inflamed tissue sites, poor ability or failure to regenerate from thymic precursor cells, lack of antigen-presenting cells (APCs), or MAIT cell death caused by MR1-dependent antigen-induced cell death (AICD), activation-induced apoptosis, bystander cell death and direct viral infection [28]

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) infection leads to dramatic loss of CD4+ T cells and increased systemic T-cell activation contributing to increased susceptibility to opportunistic infections (OIs), especially with Mycobacterium tuberculosis (MTB) [1,2,3]. Clinical evidence suggests that despite long-term highly-active antiretroviral treatment (HAART), susceptibility to MTB infection is not fully repaired, and that loss of the CD4+ T cells is not the sole responsible mechanism [5, 6]. MAIT cells express a semi-invariant Vα7.2-Jα33/12/20 T-cell receptor (TCR) that recognize antigens presented on the MHC class I-related (MR1) molecule [7, 9, 10]. The CD161++CD8+ T cells reportedly produce IL-17A and IL-22, factors important in the maintenance of mucosal integrity and antibacterial immune responses [9, 16,17,18]. MAIT cells appear to have a role in host immune responses against MTB [15, 24]

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