bims-maitce 2025-11-16 papers

Issue of 2025–11–16
four papers selected by
Andy E. Hogan, Maynooth University

J Immunol. 2025 Nov 09. pii: vkaf260. [Epub ahead of print]

CD4+ mucosal-associated invariant T cells express highly diverse T cell receptors.

Rimanpreet Kaur, Danielle Xie, Atul Pradhan, Nezar Mehanna, Kelin Li, Jeffrey Aubé, Barbara Rosati, David Carlson, Christina Y Lee, Charles Kyriakos Vorkas.

Mucosal-associated invariant T (MAIT) 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 in humans express a conserved CD8αβ+ TRAV1-2 T cell receptor (TCR) recognizing microbially derived vitamin B2 intermediates presented by the evolutionarily conserved major histocompatibility complex class I-related molecule, MR1, there is an emerging appreciation for diverse MAIT cell subsets that possess distinct functions including CD4+ MAIT cells that remain underexplored. In this study, we adopted an unbiased single-cell TCR-sequencing approach in MR1-5-OP-RU-tetramer-reactive T cells. We discovered that CD4+ MAIT cells are enriched with highly diverse TRAV1-2- TCRs. To specifically characterize this TCR repertoire, we analyzed VDJ sequences across 2 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 segment, CDR3α, and TRBV sequences. TRAV1-2- MAIT cell TCRs were also enriched after in vitro culture with interleukin-2 and Mycobacterium 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 for them.

Keywords: CD4+ MAIT cells; CITE-Seq; TCR diversity; innate lymphocytes; single cell genomics

DOI: https://doi.org/10.1093/jimmun/vkaf260

Sci Rep. 2025 Nov 13. 15(1): 39822

Diagnostic accuracy of interferon-gamma release assay and mucosal-associated invariant T cells in spinal tuberculosis.

Korawish Mekariya, Pisanukiet Saneewong Na Ayutthaya, Akkaraporn Naowanirut, Artit Wongsa, Boonrat Tassaneetrithep, Wiwit Tantibhedhyangkul, Popchai Ngamskulrungroj, Sorranart Muangsomboon, Pipat Cheiwvit, Sirichai Wilartratsami, Panya Luksanapruksa, Nasuda Danchaivijitr, Kitidete Boonchai, Apisit Rattanatanasarn, Monchai Ruangchainikom.

Conventional diagnostic methods for tuberculous spondylodiscitis (TS) require tissue biopsy, which can delay diagnosis. Immunodiagnostic approaches, including interferon-gamma release assays (IGRAs), have shown potential for improving TS diagnosis. Recent advancements have also identified the potential role of mucosal-associated invariant T (MAIT) cells as biomarkers for TB infection. This study aims to evaluate the diagnostic performance of IGRA using the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and MAIT cell analysis for diagnosing TS. Sixty-five patients suspected TS were prospectively enrolled, of whom 24 (37%) were categorized as confirmed TS. QFT-GIT demonstrated a sensitivity of 82.61% and specificity of 77.78%. No significant differences were found in the proportion of MAIT cells, CD4 + MAIT, CD8 + MAIT, and Double negative (CD4- CD8-) MAIT when compared between TS and non-TS patients. However, The MAIT cell population in CD8 + T lymphocytes subset was significantly higher in patients with TS (p = 0.0081). MAIT cell percentage > 2.63% in CD8 + T cell subset demonstrated fair discriminative ability, with an AUC of 0.746, sensitivity of 90.5%, and specificity of 51.4%. Combining QFT-GIT and the proportion of MAIT cells in CD8 + T cells subset improved specificity to 96.9%. These findings highlight the potential of these tests as promising, non-invasive diagnostic tools for differentiating TS in spondylodiscitis patients, especially when tissue diagnosis is not feasible.

Keywords: Diagnostic tests; Interferon-gamma release assays; MAIT cells; Mucosal-Associated invariant t cells; Spinal tuberculosis; Spondylitis tuberculous

DOI: https://doi.org/10.1038/s41598-025-23408-x

Immunology. 2025 Nov 12.

Selective Reduction of MAIT Cells in Peripheral Blood T Cell Subsets of Primary Sjögren's Syndrome and Their Clinical Significance.

Zhao Guan, Bohao Yang, Hanxi Luo, Zhenxue Li, Zhiwei Zong, Jie Chen, Weijie Lin, Bing Shen, Ziqi Xiong, Chen Liu.

This study aims to assess the distribution of mucosal-associated invariant T (MAIT) cells across CD3+ T cell subsets in human peripheral blood and investigate their changes in patients with primary Sjögren's syndrome (pSS), exploring their potential clinical implications. Peripheral blood from 39 pSS patients and 45 healthy controls was analysed. CD3+ T cells were categorised into four subsets: CD4+CD8-, double-positive (DP), double-negative (DN), and CD8+CD4-. MAIT cells (CD161++TCRVα7.2+) were identified using flow cytometry. Proportions and absolute counts of MAIT cells were compared between pSS patients and controls. Supplementary experiments were conducted on the peripheral blood of 15 pSS patients and 17 healthy controls to analyse the expression of GZMB and perforin in MAIT cells and their four subpopulations (CD4+ MAIT, CD8+ MAIT, DN MAIT, and DP MAIT). MAIT cell-related parameters were correlated with clinical indices, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The proportion and absolute count of MAIT cells were significantly reduced in pSS patients compared to healthy controls. In particular, MAIT cell levels were markedly lower in the DN and CD8+CD4- subsets. Additionally, the absolute counts of MAIT cells were significantly decreased in the DP, DN, and CD8+CD4- subsets, whereas no significant change was observed in the CD4+CD8- subset. Compared with healthy controls, the proportion of GZMB+ cells in the CD8+ MAIT and DN MAIT subpopulations of pSS patients increased. The percentages of MAIT cells within CD3+ T cells were negatively correlated with inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-SSB antibodies. Notably, MAIT cells in the DN subset were also positively correlated with complement C4 levels. MAIT cell proportions and counts vary across CD3+ T cell subsets, showing significant reductions in pSS patients. These findings highlight the potential role of MAIT cells as a diagnostic biomarker, given their strong associations with clinical disease markers in pSS.

Keywords: MAIT cells; T cell subsets; diagnostic biomarker; primary Sjögren's syndrome

DOI: https://doi.org/10.1111/imm.70062

Front Immunol. 2025 ;16 1667186

Multi-omic analysis of PBMCs in sepsis reveals widespread cytotoxic dysfunction and an increased population of CD69 expressing naïve CD4+ T cells.

Joshua Flynn, Anne Marie Baird, Eamon Breen, Michael Carty, Ciara S McNevin, Lisa McDermott, Elaine M Kenny, John Davis Coakley, Thomas Ryan, Derek G Doherty, Orla Sheils.

Introduction: Sepsis is responsible for 1 in 5 deaths globally and the majority of those who survive have lasting health issues. A hallmark of sepsis is a deregulated inflammatory response to infection, with leukocytes playing a critical role.
Methods: This study utilised a targeted single-cell multi-omics approach to characterise peripheral blood mononuclear cell (PBMC) populations and their transcriptomic profiles in an Irish cohort of people with (i) sepsis and (ii) bacteraemia without sepsis (defined as clinically significant positive blood culture without sepsis as assessed by the Clinical Microbiology service).
Results: Variable leukocyte distributions were identified, with decreased cytotoxic lymphocytes, including CD8+ T cells, natural killer cells, CD56+ T cells, γδ T cells, mucosal-associated invariant T cells, and increased T helper (Th) cell subsets within sepsis samples. Additionally, PBMCs from sepsis samples displayed an impaired expression profile in effector T cells, resulting in widespread suppression of PBMC cytotoxic activity.
Discussion: These results identify potential mechanisms underlying the functional impairment witnessed in sepsis. Such mechanisms may inform future diagnostic and treatment strategies.

Keywords: cytotoxicity; immunosuppression; inflammation; multi-omic; sepsis; single-cell sequencing

DOI: https://doi.org/10.3389/fimmu.2025.1667186