Mucosal‐associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non‐lineage‐specific (surrogate) markers such as ...anti‐TRAV1‐2, CD161, IL‐18Rα and CD26. The development of MR1‐Ag tetramers now permits the specific identification of MAIT cells based on T‐cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL‐17A, the CD4+ population produced more IL‐2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramer+ MAIT cells, with the exception of CD4+ MAIT cells, increased from birth to about 25 years of age and declined thereafter. We also demonstrate a positive association between the frequency of MAIT cells and other unconventional T cells including Natural Killer T (NKT) cells and Vδ2+ γδ T cells. Accordingly, this study demonstrates that MAIT cells are phenotypically and functionally diverse, that surrogate markers may not reliably identify all of these cells, and that their numbers are regulated in an age‐dependent manner and correlate with NKT and Vδ2+ γδ T cells.
This study uses MR1 tetramers to enumerate and phenotypically characterize human blood MAIT cells, and subsets thereof based on CD4 and CD8 expression. Furthermore MR1 tetramers are compared to the commonly used mAb‐based MAIT cell identification techniques.
When it’s good to have MAITs Souter, Michael NT; McCluskey, James; Corbett, Alexandra J
Immunology and cell biology,
November‐December 2020, Volume:
98, Issue:
10
Journal Article
Peer reviewed
Open access
This article discusses mucosal‐associated invariant T‐cell prophylactic and therapeutic vaccination schemes tested by Sakai et al. in mouse models of Mycobacterium tuberculosis infection together ...with the outcomes and observations.
Mucosal‐associated invariant T (MAIT) cells are a major subset of innate‐like T cells mediating protection against bacterial infection through recognition of microbial metabolites derived from ...riboflavin biosynthesis. Mouse MAIT cells egress from the thymus as two main subpopulations with distinct functions, namely, T‐bet‐expressing MAIT1 and RORγt‐expressing MAIT17 cells. Previously, we reported that inducible T‐cell costimulator and interleukin (IL)‐23 provide essential signals for optimal MHC‐related protein 1 (MR1)‐dependent activation and expansion of MAIT17 cells in vivo. Here, in a model of tularemia, in which MAIT1 responses predominate, we demonstrate that IL‐12 and IL‐23 promote MAIT1 cell expansion during acute infection and that IL‐12 is indispensable for MAIT1 phenotype and function. Furthermore, we showed that the bias toward MAIT1 or MAIT17 responses we observed during different bacterial infections was determined and modulated by the balance between IL‐12 and IL‐23 and that these responses could be recapitulated by cytokine coadministration with antigen. Our results indicate a potential for tailored immunotherapeutic interventions via MAIT cell manipulation.
Mucosal‐associated invariant T (MAIT) cells in mice exist as two subsets: T‐bet‐expressing MAIT1 and RORγt‐expressing MAIT17 cells. We show that interleukin (IL)‐12 and IL‐23 promote MAIT1 cell expansion during acute infection with Francisella tularensis, and that the bias toward MAIT1 or MAIT17 responses seen during different bacterial infections is determined by the balance between these cytokines. Excitingly, these responses can be recapitulated by varying the ratio of cytokines coadministered with antigen, indicating a potential for therapeutic manipulation of MAIT cells.
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