Human blood MAIT cell subsets defined using MR1 tetramers

Abstract

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 TCR 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 CD4fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL-17A, the CD4population produced more IL-2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramerMAIT cells, with the exception of CD4MAIT 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 Vδ2γδ 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 Vδ2γδ T cells. This article is protected by copyright. All rights reserved