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Invariant natural killer T (iNKT) cells differentiate into at least three distinct subsets within the thymus, with each subset's frequency varying considerably among mouse strains; however, the molecular mechanisms involved remain unclear. We herein report that iNKT cell lineage diversity results from the significant expansion of iNKT2 cells with limited T cell receptor (TCR) diversity in BALB/c mice and the selection of iNKT1 cells with significantly diverse TCRs in B6 mice. Furthermore, signaling lymphocytic-activation molecule family 6 (SLAMF6) expression on immature thymocytes significantly differs among mouse strains, with the low expression of SLAMF6 on BALB/c immature thymocytes resulting in high "basal TCR signaling" in preselected DP thymocytes, associated with iNKT cell expansion. Our data suggest that the expression level of SLAMF6 on immature thymocytes affects basal TCR signaling in preselected DP thymocytes, which may influence thymocyte development in a T-cell subset.
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http://dx.doi.org/10.1093/intimm/dxaf030 | DOI Listing |
J Immunol
September 2025
Department of Medical Microbiology and Immunology, 6-25 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada.
The γδ TCR instructively directs both lineage specification and effector programming of developing γδ T cells. However, the way in which different TCR signal strengths and other auxiliary signals coordinate downstream of the γδ TCR to regulate γδ T-cell development remains unclear. In this study we defined the role of Ras guanyl-releasing protein 1 (RasGRP1) in the development and effector programming of γδ T cells.
View Article and Find Full Text PDFArch Immunol Ther Exp (Warsz)
January 2025
Professor Emeritus from the Ludwik Hirszfeld, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
A narrative from a co-author of studies explaining the cellular mechanisms of self/nonself discrimination by the immune system, set against the backdrop of significant advancements in immunology during the last quarter of the 20th century. This review focuses on demonstrating the functional diversity of T cells by identifying their two major subsets: regulatory CD4 and cytotoxic CD8. It also examines the first T-cell receptor (TCR) transgenic mice, providing definitive evidence for both positive and negative selection of immature thymocytes as mechanisms for generating a self-tolerant and MHC-restricted TCR repertoire.
View Article and Find Full Text PDFNat Commun
July 2025
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Clonal deletion through negative selection is critical to eliminate autoreactive T cells in the thymus. Negative selection, however, is imperfect such that some autoreactive thymocytes can escape thymic deletion and successfully populate peripheral tissues. This is also the case for autoreactive 2D2 TCR transgenic T cells, a widely employed mouse model in studying the pathogenesis of CD4 T cell-mediated experimental autoimmune encephalomyelitis.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
August 2025
Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Background: The discovery of immune checkpoints links autoimmunity and cancer, with thymus atrophy reportedly causing autoimmune multiorgan inflammation. The impact of cancer cachexia on thymic involution and its clinical significance remains unclear. This study aimed to investigate this effect and its association with immune checkpoint inhibitor (ICI) treatment.
View Article and Find Full Text PDFCytometry B Clin Cytom
July 2025
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive neoplasm of immature T cells. Flow cytometry plays a critical role in the diagnosis and management of the disease. It is used to establish the abnormal immature T-cell phenotype and to distinguish the early T-cell precursor (ETP)-ALL from more mature types at diagnosis.
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