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Costimulation blockade: the next generation.
Curr Opin Organ Transplant
January 2025
Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia, USA.
Purpose Of The Review: Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.
Recent Findings: Emerging therapies target more specific pathways to improve efficacy and accessibility.
Mixed radiation with different doses induces CCL17 to recruit CD8T cell to exert anti-tumor effects in non-small cell lung cancer.
Front Immunol
January 2025
Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Background: Different doses of radiotherapy (RT) exert diverse effects on tumor immunity, although the precise irradiation method remains unknown. This study sought to elucidate the influence of combining different doses of RT with immune checkpoint inhibitors (ICIs) on the infiltration of CD8T cells within tumors, thereby augmenting the anti-tumor response.
Methods: Constructing a mouse model featuring bilateral lung cancer tumors subjected to high and low dose irradiation, the analysis of RNA transcriptome sequencing data and immunohistochemical validation for tumors exposed to various dosages guided the selection of the optimal low-dose irradiation scheme.
Increasing robustness of assay for immnosuppressive effect of mesenchymal stromal/stem cells: The role of inflammatory cytokine production by peripheral blood mononuclear cells.
Regen Ther
March 2025
Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki Ward, Kawasaki City, Kanagawa, 210-9501, Japan.
Introduction: The Quality by Design (QbD) approach for developing cell therapy products using mesenchymal stromal/stem cells (MSCs) is a promising method for designing manufacturing processes to improve the quality of MSC products. It is crucial to ensure the reproducibility and robustness of the test system for evaluating critical quality attributes (CQAs) in the QbD approach for manufacturing of pharmaceutical products. In this study, we explored the key factors involved in establishing a robust evaluation system for the immunosuppressive effect of MSCs, which can be an example of a CQA in developing and manufacturing therapeutic MSCs for treating graft-versus-host disease, , and we have identified method attributes to increase the robustness of a simple assay to assess the immunosuppressive effects of MSCs.
View Article and Find Full Text PDFNLRX1 limits inflammatory neurodegeneration in the anterior visual pathway.
J Neuroinflammation
January 2025
Department of Neurology, Division of Neuroimmunology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21287, USA.
Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple experimental autoimmune encephalomyelitis (EAE) models, we discovered that NLRX1 protects neurons in the anterior visual pathway from inflammatory neurodegeneration. We quantified retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1 and wild-type (WT) EAE mice and found increased RGC loss and axonal injury in Nlrx1 mice compared to WT mice in both active immunization EAE and spontaneous opticospinal encephalomyelitis (OSE) models.
View Article and Find Full Text PDFIncreases in the susceptibility of human endometrial CD4 T cells to HIV-1 infection post-menopause are not dependent on greater viral receptor expression frequency.
Front Immunol
January 2025
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
Epidemiological evidence suggests that post-menopausal women are more susceptible to HIV infection following sexual intercourse than are younger cohorts for reasons that remain unclear. Here, we evaluated how menopause-associated changes in CD4 T cell numbers and subsets as well as HIV coreceptor expression, particularly CCR5, in the endometrium (EM), endocervix (CX), and ectocervix (ECX) may alter HIV infection susceptibility. Using a tissue-specific mixed cell infection model, we demonstrate that while no changes in CD14 macrophage infection susceptibility were observed, CD4 T cell HIV-1 infection frequency increases following menopause in the EM, but not CX nor ECX.
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