bims-maitce 2025-04-20 papers

Issue of 2025–04–20
three papers selected by
Andy E. Hogan, Maynooth University

Oxf Open Immunol. 2025 ;6(1): iqaf002

Mucosal-associated invariant T (MAIT) cell responses in Salmonella enterica serovar Typhi strain Ty21a oral vaccine recipients.

Shubhanshi Trivedi, Olivia J Cheng, Ben J Brintz, Richelle C Charles, Daniel T Leung.

Mucosal-associated invariant T (MAIT) cells are unconventional innate-like T cells abundant in human mucosal tissues and are associated with protective responses to microbial infections. MAIT cells have the capacity for rapid effector functions, including the secretion of cytokines and cytotoxic molecules. In this study, we examined the longitudinal circulating MAIT cell response to the live attenuated oral vaccine Ty21a (Ty21a) against Salmonella enterica serovar Typhi (S. Typhi). We enrolled healthy adults who received a course of oral live-attenuated S. Typhi strain Ty21a vaccine and assessed peripheral blood MAIT cell longitudinal responses pre-vaccination, and at seven days and one-month post-vaccination, using flow cytometry, cell migration, and tetramer decay assays. We showed that following vaccination, circulating MAIT cells were lower in frequency, but were more activated, and had higher levels of gut-homing marker integrin α4β7 and chemokine receptors CCR9 and CCR6, suggesting the potential of MAIT cells to migrate to mucosal sites. We found no significant differences in MAIT cell functionality, cytotoxicity and T-cell receptor avidity, except in TNF expression, which was higher post-vaccination. We show that MAIT cell immune responses are modulated post-vaccination against S. Typhi. This study contributes to our understanding of MAIT cells' potential role in oral vaccination against bacterial mucosal pathogens.

Keywords: Mucosal-associated invariant T (MAIT) cells; Salmonella enterica serovar Typhi; chemokine receptors; mucosal tissue; typhoid fever; vaccination; vaccine

DOI: https://doi.org/10.1093/oxfimm/iqaf002

Res Sq. 2025 Apr 01. pii: rs.3.rs-6265058. [Epub ahead of print]

Human Neonatal MR1T Cells Have Diverse TCR Usage, are Less Cytotoxic and are Unable to Respond to Many Common Childhood Pathogens.

Deborah A Lewinsohn, Dylan Kain, Wael Awad, G W McElfresh, Meghan Cansler, Gwendolyn Swarbrick, Kean Poa, Conor McNeice, Gregory Boggy, Katherine Rott, Megan Null, David Lewinsohn, Jamie Rossjohn, Benjamin Bimber.

Neonatal sepsis is a leading cause of childhood mortality. Understanding immune cell development can inform strategies to combat this. MR1-restricted T (MR1T) cells can be defined by their recognition of small molecules derived from microbes, self, and drug and drug-like molecules, presented by the MHC class 1-related molecule (MR1). In healthy adults, the majority of MR1T cells express an invariant α-chain; TRAV1-2/TRAJ33/12/20 and are referred to as mucosal-associated invariant T (MAIT) cells. Neonatal MR1T cells isolated from cord blood (CB) demonstrate more diversity in MR1T TCR usage, with the majority of MR1-5-OP-RU-tetramer(+) cells being TRAV1-2(-). To better understand this diversity, we performed single-cell-RNA-seq/TCR-seq (scRNA-seq/scTCR-seq) on MR1-5-OP-RU-tetramer(+) cells from CB (n=5) and adult participants (n=5). CB-derived MR1T cells demonstrate a less cytotoxic/pro-inflammatory phenotype, and a more diverse TCR repertoire. A panel of CB and adult MAIT and TRAV1-2(-) MR1T cell clones were generated, and CB-derived clones were unable to recognize several common riboflavin-producing childhood pathogens (S. aureus, S. pneumoniae, M. tuberculosis). Biochemical and structural investigation of one CB MAIT TCR (CB964 A2; TRAV1-2/TRBV6-2) showed a reduction in binding affinity toward the canonical MR1-antigen, 5-OP-RU, compared to adult MAIT TCRs that correlated with differences in β-chain contribution in the TCR-MR1 interface. Overall, this data shows that CB MAIT and TRAV1-2(-) MR1T cells, express a diverse TCR repertoire, a more restricted childhood pathogen recognition profile and diminished cytotoxic and pro-inflammatory capacity. Understanding this diversity, along with the functional ability of TRAV1-2(-) MR1T cells, could provide insight into increased neonatal susceptibility to infections.

DOI: https://doi.org/10.21203/rs.3.rs-6265058/v1

Transl Cancer Res. 2025 Mar 30. 14(3): 1995-2009

Biological and clinical significance of circulating mucosal-associated invariant T cells in lung cancer.

Jingjing Liu, Haoyu Wang, Xiaotao Wang, Jacek Jassem, Jiming Si, Yuanhua Liu, Jianjun Jin.

Background: Lung cancer is among the most common malignant tumors worldwide. Circulating mucosal-associated invariant T (cMAIT) cells play an important role in cancer. This study investigated the biological and clinical significance of cMAIT cells in lung cancer.
Methods: Fasting peripheral blood mononuclear cells (PBMCs) were extracted from 30 newly diagnosed lung cancer patients and 30 healthy controls. The percentages of cMAIT among the CD3+T cells, their absolute values, and subpopulation distribution in both groups were compared by flow cytometry. The correlations of cMAIT with the neutrophil-to-lymphocyte ratio (NLR) and the expression of programmed cell death-ligand 1 (PD-L1) were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma interleukin-6 (IL-6), interleukin-8 (IL-8), and interferon-γ (IFN-γ) levels in lung cancer patients and healthy controls. The percentage of MAIT cells in the tumor tissues and adjacent normal lung tissues was measured by flow cytometry.
Results: The percentages and absolute values of the cMAIT in lung cancer patients were lower than in healthy subjects (P<0.001, P<0.01, respectively). The CD8+CD4- subgroup was dominant in both groups. There was no significant difference in percentages of the CD8+CD4- subgroup between lung cancer patients and healthy subjects (P=0.63), but the absolute values of CD8+CD4- cells were lower in lung cancer patients (P<0.05). The percentages and absolute values of cMAIT in lung cancer patients were negatively correlated with NLR (r=-0.537; P<0.01 and r=-0.423; P<0.05, respectively). The cMAIT cell percentage did not correlate with PD-L1 tumor expression (r=-0.1740; P=0.59) and with the PD-L1 expression level (P>0.99). No differences were found in the plasma IL-6, IL-8, and IFN-γ levels in lung cancer patients and healthy controls (P=0.63, P=0.052, P=0.13, respectively). The percentage of mucosal-associated invariant T (MAIT) cells in lung cancer tissues was higher than in the adjacent normal lung tissues (1.44% vs. 1.29%, P=0.044).
Conclusions: Lower percentage and absolute values of cMAIT in lung cancer patients may be due to their migration into tissues. The number of cMAIT in lung cancer patients may potentially be considered as a prognostic indicator.

Keywords: Mucosal-associated invariant T cells (MAIT cells); lung cancer; prognosis

DOI: https://doi.org/10.21037/tcr-2025-178