Journal article

The CD4−CD8− MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8 MAIT cell pool

J Dias, C Boulouis, JB Gorin, RHGA Van Den Biggelaar, KG Lal, A Gibbs, L Loh, MY Gulam, WR Sia, S Bari, WYK Hwang, DF Nixon, S Nguyen, MR Betts, M Buggert, MA Eller, K Broliden, A Tjernlund, JK Sandberg, E Leeansyah

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2018

Abstract

Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8α coreceptor (CD8+), with a smaller subset lacking both CD4 and CD8 (double-negative, DN). However, it is unclear if these two MAIT cell subpopulations distinguished by CD8α represent functionally distinct subsets. Here, we show that the two MAIT cell subsets express divergent transcriptional programs and distinct patterns of classic T cell transcription factors. Furthermore, CD8+ MAIT cells have higher levels of receptors for IL-12 and IL-18, as well as of the activating ..

View full abstract

University of Melbourne Researchers

Grants

Awarded by H2020 Marie Skłodowska-Curie Actions


Funding Acknowledgements

We thank Asa-Lena Dackland and Dr. Iyadh Douagi (Karolinska Institutet) and Charles K. L. Lou and Charlene S. F. Foong (Singapore Health Services) for their technical assistance with FACS-sorting experiments; and Dohoon Kim (Walter Reed Army Institute of Research) for assisting in Fluidigm Biomark gene-expression analyses. The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie; and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. This research was supported by Swedish Research Council Grant 2015-00174; Marie Sklodowska Curie Actions; Cofund; Project INCA 600398; the Jonas Soderquist Foundation for Virology and Immunology; the Erik and Edith Fernstrom Foundation for Medical Research; the Swedish Society of Medicine (E.L.); and Swedish Research Council Grant 2016-03052, Swedish Cancer Society Grant CAN 2017/777, and National Institutes of Health Grant R01DK108350 (to J.K.S.). J.D. was supported by Fundacao para a Ciencia e a Tecnologia Doctoral Fellowship SFRH/BD/85290/2012, cofunded by the Programa Operacional Potencial Humano-Quadro de Referencia Estrategico Nacional and the European Social Fund.