Human CD8-negative MAIT cells are functionally distinct from CD8-positive MAIT cells — ASN Events
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  3. Human CD8-negative MAIT cells are functionally distinct from CD8-positive MAIT cells

Human CD8-negative MAIT cells are functionally distinct from CD8-positive MAIT cells (#147)

Joana Dias 1 , Caroline Boulouis 1 , Jean-Baptiste Gorin 1 , Robin H. G. A. van den Biggelaar 1 2 , Anna Gibbs 3 , Liyen Loh 4 5 , Muhammad Yaaseen Gulam 6 , Douglas F. Nixon 4 7 , Kristina Broliden 3 , Annelie Tjernlund 3 , Johan K. Sandberg 1 , Edwin Leeansyah 1 6
  1. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
  2. Department of Infectious Diseases and Immunology, Universiteit Utrecht, Utrecht, the Netherlands
  3. Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
  4. Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
  5. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia
  6. Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore
  7. Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, D. C., United States of America

Mucosa-associated invariant T (MAIT) cells are a large subset of unconventional T cells that recognise microbial riboflavin metabolites presented by the MHC class I-like protein MR1. In humans, they express the invariant TCR Vα7.2 segment, coupled with restricted Jα segments and limited Vβ repertoires, and consist of two subsets defined by the expression of the CD8α co-receptor, namely CD4- CD8+ (CD8+) and CD4- CD8- (DN) MAIT cells. There is currently scant knowledge on the biology of these two MAIT cell subsets and their relationship to each other.

In the present study, we found that these subsets displayed limited differences in their surface immunoproteome, with higher expression levels of co-stimulatory molecules on CD8+ MAIT cells being the most notable difference. However, CD8+ MAIT cells had higher basal levels of cytolytic proteins, and distinct expression patterns of classical T cell transcription factors. Such differences were more pronounced in mucosal tissue-derived CD8+ MAIT cells, and appeared linked to enhanced functionality of CD8+ MAIT cells following stimulations with riboflavin-autotrophic and -auxotrophic Escherichia coli strains and mitogens. Interestingly, DN MAIT cells had higher propensity for apoptosis both at resting state and following such stimulations.

Activation of CD8+ MAIT cells through TCR and bacterial stimulations led to the downregulation of CD8α and induced the appearance of DN MAIT cells. This process appeared to depend on presentation of riboflavin metabolite antigen by MR1. Finally, DN MAIT cells from human fetal tissues displayed a more mature phenotype and accumulated over gestational time, with reciprocal contraction of CD8+ MAIT cells during in utero development. In adult peripheral blood, DN MAIT cells expressed a more restricted Vβ repertoire and belonged as a subset of CD8+ MAIT cells’ Vβ repertoire. Overall, our study defined key biological differences of the two major subsets of human MAIT cells and their apparent derivative relationship.