Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells

Author:

Walker Lucy J.1,Kang Yu-Hoi1,Smith Matthew O.1,Tharmalingham Hannah1,Ramamurthy Narayan1,Fleming Vicki M.1,Sahgal Natasha2,Leslie Alistair3,Oo Ye4,Geremia Alessandra5,Scriba Thomas J.6,Hanekom Willem A.6,Lauer Georg M.7,Lantz Olivier8,Adams David H.4,Powrie Fiona5,Barnes Eleanor19,Klenerman Paul19

Affiliation:

1. Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;

2. Bioinformatics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;

3. Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, United Kingdom;

4. Centre for Liver Research and NIHR Biomedical Research Unit, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom;

5. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;

6. South African Tuberculosis Vaccine Initiative, School of Child and Adolescent Health and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa;

7. Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA,;

8. Département de Biologie des Tumeurs, Institut Curie, Paris, France; and

9. National Institute of Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom

Abstract

Human mucosal associated invariant T (MAIT) CD8+ and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 (++) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161++CD8αβ+ T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2+) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161++CD8+/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161++CD8αβ+ counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161++CD8+ T-cell pool and the distinct phenotype and function of CD8αα cells in man.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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