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Innate-like lymphocytes, which comprise an integral part of the immune system, possess unique developmental and functional capabilities that set them apart from conventional T and B lymphocytes. Strategically located to act as a first line of defense against pathogens, they behave as innate cells. To efficiently perform their innate functions, these populations are endowed with common phenotypic characteristics that include the expression of semi-invariant TCR or BCR and activation/memory cell markers. Moreover, they have the capacity to rapidly respond to pathogenic threats and the ability to ignite adaptive immune response in synchrony with myeloid cells. Indeed, all of these common features mirror a shared molecular program, in which Signaling Lymphocytic Activation Molecule Family (SLAMF) receptors and their cytoplasmic binding partner, the adapter signaling lymphocytic activation-associated protein (SAP), play a crucial role. Despite the extensive characterization of SLAMF molecules as a group of cell-surface receptors that regulate and interconnect both innate and adaptive immune cells, their relevance in innate-like lymphocyte ontogeny and physiology has recently taken center stage. Here, we review the current understanding of the roles SLAMF receptors and SAP adaptor molecules play in the biology of innate-like lymphocytes.
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http://dx.doi.org/10.1615/critrevimmunol.2014010538 | DOI Listing |
Front Immunol
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.
View Article and Find Full Text PDFFront Immunol
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.
View Article and Find Full Text PDFFront Immunol
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.
View Article and Find Full Text PDFNature
August 2025
Francis Crick Institute, London, UK.
B-1 cells are innate-like immune cells abundant in serosal cavities with antibodies enriched in bacterial recognition, yet their existence in humans has been controversial. The CD5 B-1a subset expresses anti-inflammatory molecules including IL-10, PDL1 and CTLA4 and can be immunoregulatory. Unlike conventional B cells that are continuously replenished, B-1a cells are produced early in life and maintained through self-renewal.
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