Functional MAIT cells are associated with reduced simian-human immunodeficiency virus infection

Abstract

Abstract Mucosa-associated invariant T-cells (MAITs) are recently characterized novel subset of innate-like T-cells that recognize microbial metabolites presented by MHC-1b-related protein MR1. The significance of MAIT cells in anti-bacterial defense is well understood but not clearly in viral infections such as SIV/HIV infection. Here, we studied the phenotype, distribution, function of MAITs and their association with viral levels during chronic SHIV infection in rhesus macaques (RM). Two groups of healthy and chronic SHIV-infected RM were characterized for MAITs in blood and tissues. Similar to human, we found a significant fraction of RM CD8+ T cells express markers CD161, TCRVα□7.2 with high levels of IL-18R, CCR6, CD28 and CD95 that correlates with MR1 tetramer. During chronic SHIV, the frequency of MAITs are enriched in blood but unaltered in rectum, which displayed higher proliferative and cytotoxic capacity. Blood and rectal MAITs correlated inversely with plasma viral RNA and correlated directly with CD4 T cells. They respond to LPS and correlates with serum flagellin levels. Tissue analysis of MAITs during chronic SHIV showed significant enrichment in non-lymphoid tissues (lung, rectum and liver) with higher levels of tissue resident markers CD69 and CD103 unlike spleen/LN. In vitro treatment with cytokines during SHIV infection revealed that IL-7 is key for their proliferation and IL-12, IL-18 are important for their cytotoxicity. Thus our results demonstrates that functional MAITs are enriched in blood and rectum during chronic SHIV infection that inversely correlates with plasma viral levels. Therapies such combined cytokines could be beneficial for enhancing functional MAIT cells during chronic HIV infection in vivo.