Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection

PLoS Pathog. 2015 Aug 21;11(8):e1005072. doi: 10.1371/journal.ppat.1005072. eCollection 2015 Aug.


Mucosa-associated invariant T (MAIT) cells represent a large innate-like evolutionarily conserved antimicrobial T-cell subset in humans. MAIT cells recognize microbial riboflavin metabolites from a range of microbes presented by MR1 molecules. MAIT cells are impaired in several chronic diseases including HIV-1 infection, where they show signs of exhaustion and decline numerically. Here, we examined the broader effector functions of MAIT cells in this context and strategies to rescue their functions. Residual MAIT cells from HIV-infected patients displayed aberrant baseline levels of cytolytic proteins, and failed to mobilize cytolytic molecules in response to bacterial antigen. In particular, the induction of granzyme B (GrzB) expression was profoundly defective. The functionally impaired MAIT cell population exhibited abnormal T-bet and Eomes expression patterns that correlated with the deficiency in cytotoxic capacity and cytokine production. Effective antiretroviral therapy (ART) did not fully restore these aberrations. Interestingly, IL-7 was capable of arming resting MAIT cells from healthy donors into cytotoxic GrzB+ effector T cells capable of killing bacteria-infected cells and producing high levels of pro-inflammatory cytokines in an MR1-dependent fashion. Furthermore, IL-7 treatment enhanced the sensitivity of MAIT cells to detect low levels of bacteria. In HIV-infected patients, plasma IL-7 levels were positively correlated with MAIT cell numbers and function, and IL-7 treatment in vitro significantly restored MAIT cell effector functions even in the absence of ART. These results indicate that the cytolytic capacity in MAIT cells is severely defective in HIV-1 infected patients, and that the broad-based functional defect in these cells is associated with deficiency in critical transcription factors. Furthermore, IL-7 induces the arming of effector functions and enhances the sensitivity of MAIT cells, and may be considered in immunotherapeutic approaches to restore MAIT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytotoxicity, Immunologic / immunology*
  • Flow Cytometry
  • HIV Infections / immunology*
  • HIV-1*
  • Humans
  • Interleukin-7 / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Mucous Membrane / immunology
  • Natural Killer T-Cells / immunology*


  • IL7 protein, human
  • Interleukin-7

Grant support

This research was supported by grants from the Swedish Research Council, the Swedish Cancer Foundation, the Petrus and Augusta Hedlund Foundation, and the Stockholm County Council (JKS). Further support came from the Lindhés Law Firm, Physicians against AIDS Foundation, the Clas Groschinsky Memorial Fund, and Swedish Society for Medicine (EL). EL was a recipient of a Swedish Institute Postdoctoral Fellowship. JD is supported by Fundação para a Ciência e a Tecnologia (SFRH/BD/85290/2012, doctoral fellowship), through program QREN-POPH-typology 4.1. JKS is a Senior Research Fellow of the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.