bims-maitce 2025-09-07 papers

Issue of 2025–09–07
four papers selected by
Andy E. Hogan, Maynooth University

Sci Immunol. 2025 Aug 29. 10(110): eadu3337

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines.

PITCH Consortium‡

Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes-mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells-which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)-mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell-derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ-licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.

DOI: https://doi.org/10.1126/sciimmunol.adu3337

J Immunol. 2025 Sep 03. pii: vkaf226. [Epub ahead of print]

CD55hi MAIT cells with elevated cytokine secretion and activation markers serve as potential diagnostic indicators in Sjögren's disease.

Yiming Gao, Hanxi Luo, Bohao Yang, Xuzheng Song, Ziqi Xiong, Ayibaota Bahabayi, Zhonghui Zhang, Chen Liu.

Mucosal-associated invariant T (MAIT) cells play a vital role in immune responses, yet their involvement in autoimmune diseases such as Sjögren's disease (SjD) remains unclear. CD55, a key regulator of complement activation, influences immune cell function. This study investigates CD55 expression on MAIT cells in SjD patients and healthy controls, evaluating its potential as a diagnostic marker. Flow cytometry was used to assess CD55 expression on MAIT cell subsets, including CD4-CD8+, CD4+CD8-, double-positive (DP), and double-negative (DN), in peripheral blood from SjD patients and healthy controls. Functional markers (PD-1, CD83, and CD44), cytokine production (TNF-α, IFN-γ, IL-17, IL-22), and granzyme B (GZMB) secretion were analyzed following 5-OP-RU and brefeldin A stimulation. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic utility of CD55 expression. CD55 was highly expressed on MAIT cells, with the highest expression intensity observed in DP MAIT cells, followed by CD4+CD8- MAIT and CD4-CD8+ MAIT, with the lowest expression found in DN MAIT cells. CD55hi MAIT cells demonstrated significantly higher percentages of PD-1+, CD83+, and CD44+ cells, along with enhanced cytokine and GZMB secretion following stimulation. In SjD patients, CD55 expression was significantly upregulated in MAIT cells. ROC analysis indicated that CD55hi MAIT cells have potential diagnostic value for SjD. CD55 is highly expressed on MAIT cells, with upregulation in SjD patients correlating with inflammation and autoantibodies, suggesting CD55hi MAIT cells as a potential diagnostic marker for SjD.

Keywords: CD55; MAIT cells; Sjögren’s disease

DOI: https://doi.org/10.1093/jimmun/vkaf226

bioRxiv. 2025 Aug 27. pii: 2025.08.22.671764. [Epub ahead of print]

MAIT cell enrichment in Lynch syndrome is associated with immune surveillance and colorectal cancer risk.

Hairu Yang, Michaela Dungan, Keely Beyries, Xin Wang, Robert Kilpatrick, Baron Chen, Sangmi Oh, Marissa Berkowitz, David Smith, Sergei B Koralov, Jordan Axelrad, Christopher J Lengner, Nicole Belle, Meenakshi Bewtra, Bryson W Katona, Ken Cadwell.

Tissue microenvironment characteristics associated with elevated risk of colorectal cancer (CRC) in Lynch syndrome (LS) are poorly characterized. We applied the multimodal single cell sequencing platform ExCITE-seq to define the colonic cellular composition and transcriptome of LS carriers with and without a history of CRC compared with general population controls. Our analysis revealed widespread remodeling in LS that included striking expansion of epithelial stem and progenitor cells, and loss of fibroblast populations. Although clonally expanded and terminally exhausted CD8 T cells were more prominent in individuals with a history of CRC, LS carriers without CRC displayed enrichment of cytotoxic mucosal-associated invariant T (MAIT) cells associated with CCL20 expression in epithelial progenitors, validated by orthogonal techniques including demonstration of a protective function in a murine model of CRC. These findings highlight cellular features that distinguish LS carriers and suggest a protective role of MAIT cells in human CRC surveillance.

DOI: https://doi.org/10.1101/2025.08.22.671764

Front Immunol. 2025 ;16 1656994

Exploring the role of unconventional T cells in rheumatoid arthritis.

Tangqing Xu, Hao Cai, Jianye Liu, Xingxing Mao, Yulong Chen, Minhao Chen, Youhua Wang.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by sustained synovial inflammation and the gradual destruction of joint structures. Although conventional T cells have historically been viewed as central to RA pathogenesis, increasing attention has recently focused on unconventional T cell subsets, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and gamma delta T (γδ T) cells. Functioning as a bridge between innate and adaptive immunity, these cells contribute to RA immunopathogenesis by producing cytokines, exerting cytotoxic effects, and interacting with various immune and stromal cells. This review offers a comprehensive analysis of the immunological characteristics and pathogenic roles of unconventional T cell subsets in RA. NKT, MAIT, and γδ T cells contribute to the amplification of inflammatory responses and joint tissue destruction through diverse mechanisms, exhibiting unique tissue tropism and functional plasticity. Recently, novel therapeutic strategies have been developed to target these subsets, including modulation of antigen presentation pathways, inhibition of pro-inflammatory signaling cascades, and reprogramming of cellular functionalities. Advancements in single-cell omics and spatial immune profiling have facilitated the precise identification and characterization of pathogenic unconventional T cell subsets in the RA synovium, thereby paving the way for personalized immunotherapeutic approaches.

Keywords: gamma delta T (γδ T) cells; mucosal-associated invariant T (MAIT) cells; natural killer T (NKT) cells; rheumatoid arthritis (RA); unconventional T cells

DOI: https://doi.org/10.3389/fimmu.2025.1656994