bims-maitce 2024-02-04 papers

Issue of 2024–02–04
three papers selected by
Andy E. Hogan, Maynooth University

JCI Insight. 2024 Feb 01. pii: e166310. [Epub ahead of print]

Human MAIT cells inhibit alloreactive T-cell responses and protect from acute graft-versus-host disease.

Nana Talvard-Balland, Marion Lambert, Mathieu F Chevalier, Norbert Minet, Marion Salou, Marie Tourret, Armelle Bohineust, Idan Milo, Véronique Parietti, Thomas Yvorra, Gérard Socié, Olivier Lantz, Sophie Caillat-Zucman.

Adoptive transfer of immune regulatory cells can prevent or ameliorate graft-versus-host disease (GVHD), which remains the main cause of non-relapse mortality after allogeneic hematopoietic stem-cell transplantation. Mucosal-associated invariant T cells (MAITs) were recently associated with tissue repair capacities and with lower rates of GVHD in humans. Here, we analyzed the immunosuppressive effect of MAITs in an in vitro model of alloreactivity and explored their adoptive transfer in a preclinical xenogeneic-GVHD model. We found that MAIT cells, whether freshly purified or shortly expanded, dose-dependently inhibited proliferation and activation of alloreactive T cells. In immunodeficient mice injected with human PBMCs, MAITs strongly delayed GVHD onset and severity when transferred early after PBMC injection, but could also control ongoing GVHD when transferred at delayed time points. This effect was associated with decreased proliferation and effector function of human T cells infiltrating tissues of diseased mice and was correlated with lower circulating IFN-γ and TNF-α levels, and increased IL-10 levels. MAITs acted partly in a contact-dependent manner, which likely required direct interaction of their TCR with MR1 induced on host-reactive T cells. These results support the setup of clinical trials using MAITs as universal therapeutic tools to control severe GVHD or mucosal inflammatory disorders.

Keywords: Immunology; Stem cell transplantation; T cells; Transplantation

DOI: https://doi.org/10.1172/jci.insight.166310

bioRxiv. 2024 Jan 19. pii: 2024.01.16.575894. [Epub ahead of print]

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth.

Olivia J Cheng, Eric J Lebish, Owen Jensen, Damian Jacenik, Shubhanshi Trivedi, Jackson Cacioppo, Jeffrey Aubé, Ellen J Beswick, Daniel T Leung.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1 -/- mice with MC38-derived tumors and tumor growth was assessed. Peritumoral injection of MAIT cells inhibits tumor growth compared to control. Genomic and multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. Multiplex cytokine and flow cytometry analyses of human peripheral leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. We documented that MAIT cells have a protective role in a murine colon cancer model, potentially involving novel eosinophil-associated mechanisms. This study provides evidence of the immune modulating potential of MAIT cells within the tumor microenvironment, leading to compositional and functional changes. Our results highlight the potential of MAIT cells for colon cancer immunotherapy.
Brief summary: In models of colon cancer, MAIT cells have anti-tumor activity, associated with increased production of proinflammatory and eosinophil-modulating cytokines.

DOI: https://doi.org/10.1101/2024.01.16.575894

iScience. 2024 Feb 16. 27(2): 108801

Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection.

Carolyn Samer, Hamish E G McWilliam, Brian P McSharry, Thilaga Velusamy, James G Burchfield, Richard J Stanton, David C Tscharke, Jamie Rossjohn, Jose A Villadangos, Allison Abendroth, Barry Slobedman.

The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 (HSV-1) infection there is a profound and rapid loss of MR1, in part due to expression of unique short 3 protein. Here we show that virion host shutoff RNase protein downregulates MR1 protein, through loss of MR1 transcripts. Furthermore, a third viral protein, infected cell protein 22, also downregulates MR1, but not classical MHC-I molecules. This occurs early in the MR1 trafficking pathway through proteasomal degradation. Finally, HSV-2 infection results in the loss of MR1 transcripts, and intracellular and surface MR1 protein, comparable to that seen during HSV-1 infection. Thus HSV coordinates a multifaceted attack on the MR1 antigen presentation pathway, potentially protecting infected cells from MAIT cell T cell receptor-mediated detection at sites of primary infection and reactivation.

Keywords: Cell biology; Immunology; Virology

DOI: https://doi.org/10.1016/j.isci.2024.108801