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Lymphocytes can be functionally partitioned into subsets belonging to the innate or adaptive arms of the immune system. Subsets of innate and innate-like lymphocytes may or may not express Ag-specific receptors of the adaptive immune system, yet they are poised to respond with innate-like speed to pathogenic insults but lack the capacity to develop classical immunological memory. These lymphocyte subsets display a number of common properties that permit them to integrate danger and stress signals dispatched by innate sensor cells to facilitate the generation of specialized effector immune responses tailored toward specific pathogens or other insults. In this review, we discuss the functions of distinct subsets of innate and innate-like lymphocytes. A better understanding of the mechanisms by which these cells are activated in different contexts, their interactions with other immune cells, and their role in health and disease may inform the development of new or improved immunotherapies.
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http://dx.doi.org/10.4049/jimmunol.2200074 | DOI Listing |
Nat Rev Immunol
September 2025
La Jolla Institute for Immunology, La Jolla, CA, USA.
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.
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September 2025
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States.
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.
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September 2025
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
Human C-type lectin-like molecule CD161 is a type II transmembrane protein expressed on the surface of various lymphocytes within both the innate and adaptive immune systems. CD161 serves as a marker for innate-like T cells and IL-17-producing cells. However, the meaning of these T cells expressing CD161 has not yet been fully determined.
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September 2025
Division of Vaccinology for Clinical Development, Institute for Vaccine Research and Development, Hokkaido University (HU-IVReD), Sapporo, Japan.
Background: Memory CD8 T cells sense inflammation and rapidly produce interferon-γ (IFN-γ) independent of cognate antigens. This innate-like property, called bystander activation, is involved in early host defense before the antigen-specific memory response. However, the molecular mechanisms underlying this activation remain unknown.
View Article and Find Full Text PDFSci Immunol
August 2025
Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.
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.
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