bims-maitce 2024-07-14 papers

Issue of 2024–07–14
four papers selected by
Andy E. Hogan, Maynooth University

Front Immunol. 2024 ;15 1424987

Regulation of MAIT cells through host-derived antigens.

Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells that function at the interface between innate and acquired immunity. MAIT cells recognize vitamin B2-related metabolites produced by microbes, through semi-invariant T cell receptor (TCR) and contribute to protective immunity. These foreign-derived antigens are presented by a monomorphic antigen presenting molecule, MHC class I-related molecule 1 (MR1). MR1 contains a malleable ligand-binding pocket, allowing for the recognition of compounds with various structures. However, interactions between MR1 and self-derived antigens are not fully understood. Recently, bile acid metabolites were identified as host-derived ligands for MAIT cells. In this review, we will highlight recent findings regarding the recognition of self-antigens by MAIT cells.

Keywords: MAIT cell; MR1 ligand; T cell development; bile acids; self-antigen

DOI: https://doi.org/10.3389/fimmu.2024.1424987

Front Cardiovasc Med. 2024 ;11 1385457

RNAseq of INOCA patients identifies innate, invariant, and acquired immune changes: potential autoimmune microvascular dysfunction.

Kevin Jaatinen, Palak Shah, Ramesh Mazhari, Zane Hayden, Richard Wargowsky, Tisha Jepson, Ian Toma, John Perkins, Timothy A McCaffrey.

Background: Ischemia with non-obstructive coronary arteries (INOCA) is a major clinical entity that involves potentially 20%-30% of patients with chest pain. INOCA is typically attributed either to coronary microvascular disease and/or vasospasm, but is likely distinct from classical coronary artery disease (CAD).
Objectives: To gain insights into the etiology of INOCA and CAD, RNA sequencing of whole blood from patients undergoing both stress testing and elective invasive coronary angiography (ICA) was conducted.
Methods: Stress testing and ICA of 177 patients identified 40 patients (23%) with INOCA compared to 39 controls (stress-, ICA-). ICA+ patients divided into 38 stress- and 60 stress+. RNAseq was performed by Illumina with ribosomal RNA depletion. Transcriptome changes were analyzed by DeSeq2 and curated by manual and automated methods.
Results: Differentially expressed genes for INOCA were associated with elevated levels of transcripts related to mucosal-associated invariant T (MAIT) cells, plasmacytoid dendritic cells (pcDC), and memory B cells, and were associated with autoimmune diseases such as rheumatoid arthritis. Decreased transcripts were associated with neutrophils, but neutrophil transcripts, per se, were not less abundant in INOCA. CAD transcripts were more related to T cell functions.
Conclusions: Elevated transcripts related to pcDC, MAIT, and memory B cells suggest an autoimmune component to INOCA. Reduced neutrophil transcripts are likely attributed to chronic activation leading to increased translation and degradation. Thus, INOCA could result from stimulation of B cell, pcDC, invariant T cell, and neutrophil activation that compromises cardiac microvascular function.

Keywords: INOCA; MAIT (mucosal-associated invariant T) cell; RNAseq; T cell; coronary artery disease; invasive coronary angiography (ICA); neutrophil; plasmacytoid dendritic cell

DOI: https://doi.org/10.3389/fcvm.2024.1385457

J Immunol. 2024 Jul 10. pii: ji2400045. [Epub ahead of print]

Cutting Edge: Redundant Roles for MHC Class II-, CD1d-, and MR1-restricted T Cells in Clearing Bartonella Infection.

Lena K Siewert, Katja Fromm, Christoph Dehio, Daniel D Pinschewer.

The importance of unconventional T cells for mucosal immunity is firmly established but for systemic bacterial infection remains less well defined. In this study, we explored the role of various T cell subsets in murine Bartonella infection, which establishes persistent bacteremia unless controlled by antibacterial Abs. We found that αβ T cells are essential for Ab production against and clearance of B. taylorii, whereas MHC class I (MHC-I)- or MHC class II (MHC-II)-deficient mice eliminated B. taylorii infection with normal kinetics. Similarly, animals lacking either CD1d or MR1 suppressed bacteremia with normal kinetics. Interestingly, mice with a combined deficiency of either MHC-II and CD1d or MHC-II and MR1 failed to clear the infection, indicating that the combination of CD1d- and MR1-restricted T cells can compensate for the lack of MHC-II in this model. Our data document a previously underappreciated contribution of unconventional T cells to the control of systemic bacterial infection, supposedly as helper cells for antibacterial Ab production.

DOI: https://doi.org/10.4049/jimmunol.2400045

J Immunol Methods. 2024 Jul 09. pii: S0022-1759(24)00111-X. [Epub ahead of print] 113726

A 38-colour high dimensional immunophenotyping panel for human peripheral blood mononuclear cells.

Jeremy Anderson, Leanne Quah, Kiara Mangano, Daniel G Pellicci, Nadia Mazarakis, Paul V Licciardi.

High dimensional immunophenotyping panels are invaluable resources for performing extensive phenotyping on peripheral blood mononuclear cells (PBMCs). We designed a 38-colour high dimensional phenotyping panel to measure innate (monocytes, dendritic cells, NK cells, basophils, innate like lymphoid cells), T cell (γδ T cells, MAIT cells, CD4 and CD8 memory, Th1, Th2, Th17, Tfh, Treg) and B cell (memory, plasma cells, transitional B cells, plasmablasts, IgG, IgM) subsets in addition to their activation status using the 5-laser Cytek Aurora. We optimised optimal fluorochrome combinations and titres to minimise spread and autofluorescence of rare immune cell populations and tested this panel on PBMCs from 15 healthy adults. This high dimensional panel will be invaluable for direct ex vivo studies to evaluate immune cells in the context of human health and disease, especially when samples are limited.

Keywords: Adaptive; Flow cytometry; Innate; Phenotyping

DOI: https://doi.org/10.1016/j.jim.2024.113726