HIV-Infected Children Have Lower Frequencies of CD8+ Mucosal-Associated Invariant T (MAIT) Cells that Correlate with Innate, Th17 and Th22 Cell Subsets

Alka Khaitan,Fatma Marshed,William Borkowsky,Cihan Tastan,Mengling Liu,Adam Kravietz,Max Kilberg,Derya Unutmaz,Tiina Ilmet,Mussa Mwamzuka,Aabid Ahmed,Johan K Sandberg

doi:10.1371/journal.pone.0161786

Abstract

Mucosal-associated invariant T cells (MAIT) are innate T cells restricted by major histocompatibility related molecule 1 (MR1) presenting riboflavin metabolite ligands derived from microbes. Specificity to riboflavin metabolites confers MAIT cells a broad array of host-protective activity against gram-negative and -positive bacteria, mycobacteria, and fungal pathogens. MAIT cells are present at low levels in the peripheral blood of neonates and gradually expand to relatively abundant levels during childhood. Despite no anti-viral activity, MAIT cells are depleted early and irreversibly in HIV infected adults. Such loss or impaired expansion of MAIT cells in HIV-positive children may render them more susceptible to common childhood illnesses and opportunistic infections. In this study we evaluated the frequency of MAIT cells in perinatally HIV-infected children, their response to antiretroviral treatment and their associations with HIV clinical status and related innate and adaptive immune cell subsets with potent antibacterial effector functions. We found HIV+ children between ages 3 to 18 years have significantly decreased CD8+ MAIT cell frequencies compared to uninfected healthy children. Remarkably, CD8 MAIT levels gradually increased with antiretroviral therapy, with greater recovery when treatment is initiated at a young age. Moreover, diminished CD8+ MAIT cell frequencies are associated with low CD4:CD8 ratios and elevated sCD14, suggesting a link with HIV disease progression. Last, CD8+ MAIT cell levels tightly correlate with other antibacterial and mucosa-protective immune subsets, namely, neutrophils, innate-like T cells, and Th17 and Th22 cells. Together these findings suggest that low frequencies of MAIT cells in HIV positive children are part of a concerted disruption to the innate and adaptive immune compartments specialized in sensing and responding to pathogenic or commensal bacteria.

Highlights

Mucosal-associated invariant T cells (MAIT) are a recently described unconventional T cell subset that plays an important role in antibacterial and antifungal innate immune responses in the peripheral blood and at mucosal surfaces [1,2,3]
We identified MAIT cells within CD8+ T cells by gating on CD161+Vα7.2+ cells (MAIT cells) in HIV- and HIV+ children (Fig 1A)
CD8+ T cells expressing Vα7.2 and CD161 negative cells were similar in HIV- and HIV+ children (Fig 1D) [36]

Summary

Introduction

Mucosal-associated invariant T cells (MAIT) are a recently described unconventional T cell subset that plays an important role in antibacterial and antifungal innate immune responses in the peripheral blood and at mucosal surfaces [1,2,3]. In SIV infected rhesus macaques, MAIT cells are systemically depleted in peripheral blood, mesenteric lymph nodes, and lung mucosa [37]. With their potent anti-microbial activity, this decrease of MAIT cells during HIV infection may leave individuals vulnerable to opportunistic infections such as M. tuberculosis. In addition we evaluated correlations between MAIT cell levels and innate-like T cell subsets, and other immune cells with potential antibacterial effector functions, such as Th17 cells, in perinatally HIV-infected children. CD8 MAIT cells correlated with antibacterial innate and adaptive immune subsets, namely neutrophils, γδT, NKT, Th17 and Th22 cells

Participants

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