bims-maitce 2024-08-11 papers

Issue of 2024–08–11
two papers selected by
Andy E. Hogan, Maynooth University

PLoS Pathog. 2024 Aug;20(8): e1012372

Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses.

Shivam K Purohit, Lauren Stern, Alexandra J Corbett, Jeffrey Y W Mak, David P Fairlie, Barry Slobedman, Allison Abendroth.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses.

DOI: https://doi.org/10.1371/journal.ppat.1012372

Front Immunol. 2024 ;15 1436717

Circulating MAIT cells in multiple sclerosis and amyotrophic lateral sclerosis.

Davide De Federicis, Claudia Bassani, Rosaria Rita Chiarelli, Federico Montini, Antonino Giordano, Federica Esposito, Nilo Riva, Angelo Quattrini, Vittorio Martinelli, Massimo Filippi, Cinthia Farina.

Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8+ T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8+ MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.

Keywords: CD161; MAIT cells; amyotrophic lateral sclerosis; blood; progressive multiple sclerosis

DOI: https://doi.org/10.3389/fimmu.2024.1436717