MAIT cells exercise complex functions and may be targets for future immunotherapies and vaccines

A Stony Brook University physician-scientist has identified that mucosal-associated invariant T (MAIT) cells, an unconventional form of immune cell, exercise several complex roles during healthy and disease states. The findings, published in the Journal of Immunology, the flagship journal of the American Association of Immunologists, may help to serve as a benchmark for future research on MAIT cells as targets for immunotherapies and vaccines.

In recent years, MAIT cells have received increasing attention by researchers because of their abundance in the human body, the fact that they can be rapidly activated by non-peptide vitamin intermediates from microbes, and because of their involvement in both infectious and non-infectious disease processes. Despite emerging interest in MAIT cells, it is not fully understood how they are involved in fighting disease.

We used single cell RNA sequencing technology and immunologic techniques to reveal that despite being 'one cell type with a semi-invariant T cell receptor,' MAIT cells demonstrate marked heterogeneity that recapitulates conventional T cell biology."

Charles K. Vorkas, MD, Lead Author, Assistant Professor in the Departments of Medicine, Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University

Dr. Vorkas and colleagues demonstrated in the laboratory that this marked heterogeneity includes distinct CD4⁺ and CD8⁺ lineages, as well as "killer," "helper," and "regulatory" cell phenotypes – an indication that MAIT cells exercise complex functions.

He emphasizes that in light of recent studies showing that MAIT cells respond to infectious diseases like COVID-19, as well as during inflammatory events of autoimmune disease such as in lupus, or during tumorigenesis, a better understanding of their roles will help us to develop new therapies.

Dr. Vorkas and colleagues are now trying to identify MAIT cell subpopulations responding to initial infection with Mycobacterium tuberculosis, the causative agent of TB disease, as well as to tick-borne infections endemic to Long Island. His lab hopes to harness MAIT cells and other innate lymphocyte populations to develop immunotherapeutic alternatives to antibiotic drugs and to design novel vaccines.

This work was supported by the Ludwig Center for Cancer Immunotherapy, the Tri-Institutional TB Research Unit, part of the Tuberculosis Research Units Network through National Institute of Allergy and Infectious Diseases (Grant U19AI111143), National Cancer Institute Grants (P30CA008748 and U54CA209975), a NIAID career development award( K08AI132739), and a Potts Memorial Foundation Award.