Highly differentiated CD28(-) effector T cells which accumulate in a variety of diseases and also with increasing age contribute to inflammatory processes, limit immunological space and diversity, and are associated with immunological dysfunction and reduced responses to vaccination. Elimination of CD28(-) T cells has been suggested as a measure for immunological rejuvenation but may lead to the loss of important T cell specificities. Using T cells specific for the immunodominant CMV-derived epitope NLVPMVATV as a model, we show that the same clonotypes are present in CD8(+)CD28(+) naïve/early memory and CD8(+)CD28(-) effector T cells. Therefore, CD28(-) cells do not seem to contain clones which are not present in the residual population. The elimination of effector T cells would not lead to the loss of important specificities, as relevant clonotypes could be recruited and propagated from naïve or early memory T cell subsets in the case of exposure to pathogen.
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http://dx.doi.org/10.1016/j.imlet.2009.08.008 | DOI Listing |
γδ T cells producing either interleukin-17A (γδ cells) or interferon-γ (γδ cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ cell versus γδ cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ cells versus γδ cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively.
View Article and Find Full Text PDFNat Immunol
January 2025
Department of Cardiology, Renji Hospital, School of Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China.
A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell-cell interactions during specific age.
View Article and Find Full Text PDFJ Lipid Res
January 2025
Department of Biological Sciences, Kent State University, P.O. Box 5190, Kent, OH 44242, USA. Electronic address:
Phosphatidic acid (PA) through its unique negatively charged phosphate headgroup binds to various proteins to modulate multiple cellular events. To perform such diverse signaling functions, the ionization and charge of PA's headgroup relies on the properties of vicinal membrane lipids and changes in cellular conditions. Cholesterol has conspicuous effects on lipid properties and membrane dynamics.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1; Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Electronic address:
Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.
View Article and Find Full Text PDFCell Metab
January 2025
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:
Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo.
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