The in vitro effect of seminal vesicle protein IV (SV-IV) on the cytotoxic activity of human natural or acquired cellular immunity has been investigated by standard immunological procedures, a (51)Cr-release cytotoxicity assay, and labeled-ligand binding experiments. The data obtained demonstrate that: (1) fluoresceinated or [(125)I]-labeled SV-IV binds specifically to the surface of human purified non-adherent mononuclear cells (NA-MNC); (2) SV-IV suppresses the cytotoxicity of natural killer (NK) cells against K562 target cells, that of IL-2-stimulated NK (LAK) cells against DAUDI target cells, and that of VEL antigen-sensitized cytotoxic T lymphocytes (CTLs) against VEL target cells; (3) treatment of K562 target cells alone with SV-IV decreases their susceptibility to NK-induced lysis. These findings indicate that the protein SV-IV has a marked in vitro inhibitory effect on NK, LAK and CTL cytotoxicity, providing a better understanding of its immune regulatory functions.
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http://dx.doi.org/10.1016/j.jri.2007.11.002 | DOI Listing |
J Clin Oncol
January 2025
Center for Cell Engineering, Sloan Kettering Institute, New York, NY.
Purpose: We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.
View Article and Find Full Text PDFJ Leukoc Biol
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA.
Regulated sequential exocytosis of neutrophil granules is essential in orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several pre-clinical models of inflammatory disease.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218.
The hippocampal dentate gyrus (DG) is thought to orthogonalize inputs from the entorhinal cortex (pattern separation) and relay this information to the CA3 region. In turn, attractor dynamics in CA3 perform a pattern completion or error correction operation before sending its output to CA1. In a mouse model of congenital hypoplasia of the DG, a deficiency in the (Wls) gene, specifically in cells expressing , which targets neuronal progenitors, led to an almost total absence of dentate granule cells and modestly impaired performance in spatial tasks.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Clinical Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Stem cell-based therapies have raised considerable interest to develop regenerative treatment for neurological disorders with high disability. In this review, we focus on recent preclinical and clinical evidence of stem cell therapy in the treatment of degenerative neurological diseases and discuss different cell types, delivery routes and biodistribution of stem cell therapy. In addition, recent advances of mechanistic insights of stem cell therapy, including functional replacement by exogenous cells, immunomodulation and paracrine effects of stem cell therapies are also demonstrated.
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