bims-maitce 2025-02-23 papers

Issue of 2025–02–23
three papers selected by
Andy E. Hogan, Maynooth University

bioRxiv. 2025 Feb 08. pii: 2025.02.06.636785. [Epub ahead of print]

CD4 + Mucosal-associated Invariant T (MAIT) cells express highly diverse T cell receptors.

Rimanpreet Kaur, Nezar Mehanna, Atul Pradhan, Danielle Xie, Kelin Li, Jeffrey Aubѐ, Barbara Rosati, David Carlson, Charles K Vorkas.

Mucosal-associated invariant T cells are highly conserved innate-like T cells in mammals recognized for their high baseline frequency in human blood and cytotoxic effector functions during infectious diseases, autoimmunity, and cancer. While the majority of these cells express a conserved CD8αβ+ TRAV1-2 T cell receptor recognizing microbially-derived Vitamin B2 intermediates presented by the evolutionarily conserved major histocompatibility complex I-related molecule, MR1, there is an emerging appreciation for diverse subsets that may be selected for in humans with distinct functions, including subpopulations that co-express CD4. Prior work has not examined T cell receptor (TCR) heterogeneity in CD4 + MAIT cells, largely due to bias of identifying human MAIT cells as CD8 + TRAV1-2 + cells. In this study, we adopted an unbiased single-cell TCR-sequencing approach of total MR1-5-OP-RU-tetramer-reactive T cells and discovered that CD4 + MAIT cells express highly diverse TRAV1-2 negative TCRs. To specifically characterize this TCR repertoire, we analyzed VDJ sequences of single MR1-5-OP-RU tetramer + MAIT cells across two datasets and identified distinct TCR usage among CD4 + MAIT cells including TRAV21, TRAV8 (TRAV8-1, TRAV8-2, TRAV8-3), and TRAV12 families (TRAV12-2, TRAV12-3), as well as more variable J chain and CDR3 sequences. Non-TRAV1-2 MAIT cell TCRs were also enriched after in vitro expansion, including with Mycobacterial tuberculosis . These results indicate that mature human CD4 + MAIT cells adopt distinct TCR usage from the canonical TRAV1-2 + CD8 + subset and suggest that alternative MR1 ligands in addition to riboflavin intermediates may select them.

DOI: https://doi.org/10.1101/2025.02.06.636785

J Asthma. 2025 Feb 19. 1-13

Dual Role of Mucosal-Associated Invariant T Cells (MAIT) in Asthma.

M Asghar Pasha, Rawaa K Alnabulsi, Aiden Wan, Russell J Hopp, Qi Yang.

ObjectiveMucosal-associated invariant T cells (MAIT) are the predominant type of innate-like T cells in humans, and they represent a unique subset of microbiota-dependent invariant T cells. This Commentary reviews recent clinical studies and animal model research elucidating the multifaceted roles of MAIT cells in asthma. Method: A literature search was performed using PubMed and Google Scholar, and covered the period from 1960 to 2024. The search yielded more than 50 articles, and only essential original research articles and selected review articles were evaluated. Results: Recent studies indicate that MAIT cell-derived effector molecules may play dual roles in asthma and allergic airway inflammation. While MAIT cells can produce the anti-inflammatory enzyme IL4I1 and the Th1 cytokine IFN-γ to repress allergic airway inflammation and airway hyperresponsiveness (AHR), they may also secrete IL-17. which induces neutrophil infiltration and exacerbates AHR. In addition, some clinical studies from the literature search revealed a negative association between MAIT cell abundance and asthma. Regarding allergic airway inflammation, mouse model studies suggested that MAIT cells may play a protective role. Conclusion: These findings raise critical questions as to whether MAIT cells are friend or foe in asthma, and whether distinct subsets of MAIT cells play different roles in allergic airway inflammation. Further studies are needed to better understand the implication of MAIT cells in asthma pathogenesis, particularly in patients with severe asthma.

Keywords: IL-17; airway hyper-responsiveness; allergic airway inflammation; cytokines; iNKT; microbiota; neutrophilic; severe asthma

DOI: https://doi.org/10.1080/02770903.2025.2469319

Scand J Immunol. 2025 Feb;101(2): e70008

Immune Checkpoint Receptor Expression Profiles of MAIT Cells in Moderate and Severe COVID-19.

Matyas Meggyes, David U Nagy, Ildiko Toth, Timoteus Feik, Beata Polgar, Iyad Saad Al Deen, David Sipos, Laszlo Szereday, Agnes Peterfalvi.

MAIT cells are one of the largest unconventional T cell populations and, recruited to the site of infection, play both protective and pathogenic roles during pulmonary viral infections. MAIT cell activation patterns change significantly during COVID-19, with a notable decrease in their frequency in peripheral blood of severe cases. In the present study, we aimed to investigate the expression profiles of various immune checkpoint pathways on MAIT, MAIT-like and non-MAIT cells in moderate and severe COVID-19 patients undergoing cytokine storm. Despite numerous studies comparing MAIT cell characteristics based on COVID-19 disease severity, none have delved into the critical differences in MAIT cell immune checkpoint profiles between moderate and severe COVID-19 patients, all experiencing a cytokine storm. Flow cytometry was used to analyse peripheral blood mononuclear cells from a cohort of 35 patients, comprising 18 moderate and 17 severe cases, alongside 14 healthy controls. Our investigation specifically focuses on severe COVID-19 presentations, revealing a marked deletion of MAIT cells. Further exploration into the regulatory dynamics of MAIT cell functionality reveals shifts in the expression profiles of critical immune checkpoint receptors, notably PD-1 and CD226. In severe COVID-19 patients, MAIT cells showed a significant decrease in the expression of CD226, whereas MAIT-like and non-MAIT cells demonstrated a significant increase in the expression of PD-1 compared to healthy individuals. The expression of the TIGIT receptor remained unaltered across all investigated groups. Our findings contribute to the existing knowledge by elucidating the changes in MAIT cell subpopulations and their potential role in COVID-19 disease severity.

Keywords: COVID‐19; MAIT cells; SARS‐CoV‐2; cytokine storm; disease severity; flow cytometry; immune checkpoints; viral infection

DOI: https://doi.org/10.1111/sji.70008