bims-maitce 2025-09-14 papers

Issue of 2025–09–14
two papers selected by
Andy E. Hogan, Maynooth University

Nat Rev Immunol. 2025 Sep 08.

Metabolic control of innate-like T cells.

Thomas Riffelmacher, Mitchell Kronenberg.

Immunometabolism, the intersection of cellular metabolism and immune function, has revolutionized our understanding of T cell biology. Changes in cellular metabolism help guide the development of thymocytes and the transition of T cells from naive to effector, memory and tissue-resident states. Innate-like T cells are a unique group of T cells with special characteristics. They respond rapidly, reside mainly in tissues and express T cell receptors with limited diversity that recognize non-peptide antigens. This group includes invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and some populations of γδ T cells. Different subsets of innate-like T cells rely on specific metabolic pathways that influence their differentiation and function and distinguish them from conventional CD4+ and CD8+ T cells. Although there are differences between innate-like T cell types, they share metabolic and functional features. In this Review, we highlight recent research in this emerging field. Understanding how metabolic programmes differ between innate-like T cells and other T cells may open opportunities for tailoring innate-like T cell responses and adoptive T cell therapies for use in cancer, metabolic and autoimmune diseases.

DOI: https://doi.org/10.1038/s41577-025-01219-5

Front Immunol. 2025 ;16 1628145

Cord blood innate-like T cell responses in neonates born to healthy women and women living with HIV.

David Rach, Hao-Ting Hsu, Nginache Nampota-Nkomba, Godfrey Mvula, Felix A Mkandawire, Osward M Nyirenda, Bernadette Hritzo, Francesca Boldrin, Giulia Degiacomi, Laura Cioetto Mazzabò, Riccardo Manganelli, Andrea G Buchwald, Franklin R Toapanta, Marcelo B Sztein, Miriam K Laufer, Kirsten E Lyke, Cristiana Cairo.

Innate-like T cells (ILT), including γδ T cells (Vδ2s), Natural Killer T cells (NKTs) and Mucosal-associated Invariant T cells (MAITs), integrate innate and adaptive immunity, playing important roles in homeostatic conditions as well as during infection or inflammation. ILT are present on both sides of the fetal-maternal interface, but our knowledge of their phenotypical and functional features in neonates is limited. Using spectral flow cytometry we characterized cord blood ILT in neonates born to healthy women and women living with HIV. We describe extensive phenotypic and functional heterogeneity within the cord Vδ2 cells at baseline and following activation. In neonates born to women with HIV, we observed modest differences in ILT frequencies ex-vivo and altered proportions of Vδ2 cells producing IFNγ+ or TNFα+, both ex-vivo and after expansion, compared to HIV unexposed infants. Consistent with prior studies, infants born to mothers who initiated ART before pregnancy exhibited less immune perturbation overall. Herein we expand our knowledge of ILT at the maternal-fetal interface by a comprehensive phenotypic analysis of these rare subsets.

Keywords: HIV-exposed uninfected (HEU) infants; MAIT (mucosal-associated invariant T) cell; Malawi; NKT (natural killer T) cell; cord blood (CB); gamma delta (gammadelta) T cells; intracellular cytokine staining; spectral flow cytometry

DOI: https://doi.org/10.3389/fimmu.2025.1628145