bims-maitce 2026-02-22 papers

Issue of 2026–02–22
two papers selected by
Andy E. Hogan, Maynooth University

Respir Investig. 2026 Feb 17. pii: S2212-5345(26)00020-1. [Epub ahead of print]64(2): 101386

Are there differences in antigen recognition by mucosal-associated invariant T cells against mycobacterial infection and sarcoidosis?

Yasuo Shimizu.

Mycobacterial infections and sarcoidosis have similar clinical presentations and require careful differential diagnosis, but the etiology differs between these diseases. It has been demonstrated that circulating interferon-γ levels decrease during infection by mycobacteria but increase in sarcoidosis. The involvement of innate-like lymphoid T cells in host immunity against these diseases has also become increasingly evident. Mucosal-associated invariant T (MAIT) cells are involved in innate immunity and are activated when antigens are presented to the T cell receptor through major histocompatibility complex class I-like molecules, namely MR1, by antigen-presenting cells. Notably, MAIT cells produce cytokines, such as interferon-γ, and antigen-derived ligands loaded onto MR1 can act as agonists or antagonists on MAIT cells. Therefore, MAIT cells may discriminate against ligands derived from the causative antigens of mycobacteria and sarcoidosis, potentially contributing to the ridge of the host immune response between these diseases.

Keywords: IFN-γ; MAIT; MR1; Sarcoidosis; mycobacterium

DOI: https://doi.org/10.1016/j.resinv.2026.101386

Eur J Immunol. 2026 Feb;56(2): e70154

IL-21 Selectively Augments Cytotoxic Potential of Antigen-Activated MAIT Cells.

Laura E Wedlock, Rajesh Lamichhane, Meg C Webley, Selena C L Gilmer, Andrea J Vernall, James E Ussher.

Mucosal-associated invariant T (MAIT) cells are unconventional cytotoxic T cells restricted by MHC class 1 related molecule, MR1. They are activated through their T cell receptor (TCR) by derivatives from microbial riboflavin synthesis or independently of TCR signalling via IL-12 and IL-18. Upon activation, MAIT cells upregulate cytotoxic molecules granzyme B and perforin and lyse bacterially-infected cells. While cytokines act as co-stimulatory molecules that enhance MAIT cell activation, their specific role in regulating MAIT cell cytotoxicity remains unresolved. We show that the cytokine IL-21 enhances expression of granzyme B and perforin on TCR or IL-12/IL-18-activated MAIT cells but has a limited effect on MAIT cell cytokine production. Using a flow cytometry-based cytotoxic assay, we show priming MAIT cells with IL-21 enhances their ability to kill 5-OP-RU-treated B cell lines. We demonstrate a previously unexplored co-stimulatory role for IL-21 that selectively augments the cytotoxic potential of MAIT cells.

Keywords: IL‐21; TCR activation; co‐stimulation; cytotoxicity; mucosal‐associated invariant T cells

DOI: https://doi.org/10.1002/eji.70154