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J Immunol. 2019 Apr 1;202(7):2105-2120. doi: 10.4049/jimmunol.1801405. Epub 2019 Feb 18.

MAIT Cells Upregulate α4β7 in Response to Acute Simian Immunodeficiency Virus/Simian HIV Infection but Are Resistant to Peripheral Depletion in Pigtail Macaques.

Author information

1
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia; jennifer.juno@unimelb.edu.au.
2
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Victoria 3000, Australia.
3
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Queensland 4072, Australia.
4
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Queensland 4072, Australia.
5
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Victoria 3053, Australia; and.
6
Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Victoria 3000, Australia.

Abstract

Mucosal-associated invariant T (MAIT) cells are nonconventional T lymphocytes that recognize bacterial metabolites presented by MR1. Whereas gut bacterial translocation and the loss/dysfunction of peripheral MAIT cells in HIV infection is well described, MAIT cells in nonhuman primate models are poorly characterized. We generated a pigtail macaque (PTM)-specific MR1 tetramer and characterized MAIT cells in serial samples from naive and SIV- or simian HIV-infected PTM. Although PTM MAIT cells generally resemble the phenotype and transcriptional profile of human MAIT cells, they exhibited uniquely low expression of the gut-homing marker α4β7 and were not enriched at the gut mucosa. PTM MAIT cells responded to SIV/simian HIV infection by proliferating and upregulating α4β7, coinciding with increased MAIT cell frequency in the rectum. By 36 wk of infection, PTM MAIT cells were activated and exhibited a loss of Tbet expression but were not depleted as in HIV infection. Our data suggest the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of MAIT cells during HIV infection; and 2) the lack of PTM MAIT cell enrichment at the gut mucosa may prevent depletion during chronic infection, providing a model to assess potential immunotherapeutic approaches to modify MAIT cell trafficking during HIV infection.

PMID:
30777923
DOI:
10.4049/jimmunol.1801405

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