The contribution of CCR6 and phagocyte recruitment to the initiation of T cell responses to a local pathogen is unclear. CD4 T cell activation to an injected soluble antigen occurred rapidly and was completely CCR6-independent. In marked contrast, the tempo of pathogen-specific CD4 T cell activation depended on whether the antigen was secreted or cell-associated. Furthermore, lymph node pathogen-specific CD4 T cell activation required CCR6 and cell migration from the site of infection. Surprisingly, adoptive transfer of wild-type blood phagocytes rescued bacteria-specific T cell activation in CCR6-deficient mice, even when these cells were unable to participate in direct antigen presentation. These data demonstrate that T cell responses to a local bacterial infection follow a distinct tempo, largely determined by bacterial protein secretion, and that CCR6-mediated blood phagocyte recruitment to the site of infection is a critical step in the initiation of pathogen-specific immune responses in skin draining lymph nodes.
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http://dx.doi.org/10.1073/pnas.0701363104 | DOI Listing |
Stem Cells
January 2025
Sangamo Therapeutics, 501 Canal Blvd. Richmond, CA.
iPSCs can serve as a renewable source of a consistent edited cell product, overcoming limitations of primary cells. While feeder-free generation of clinical grade iPSC-derived CD8 T cells has been achieved, differentiation of iPSC-derived CD4sp and regulatory T cells requires mouse stromal cells in an artificial thymic organoid. Here we report a serum- and feeder-free differentiation process suitable for large-scale production.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Research, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Background: Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions and neuroprotection during the acute phase, there has been a growing focus on tissue repair and functional recovery in the subacute and chronic phases after stroke. The pro-inflammatory microglial polarization occurs in subacute and chronic phases after stroke and may represent therapeutic targets for stroke recovery.
View Article and Find Full Text PDFBrain Behav Immun Health
February 2025
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases-IRCAD, University of Eastern Piedmont, 28100, Novara, Italy.
Major Depressive Disorder (MDD) is a widespread psychiatric condition impacting social and occupational functioning, making it a leading cause of disability. The diagnosis of MDD remains clinical, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, as biomarkers have not yet been validated for diagnostic purposes or as predictors of treatment response. Traditional treatment strategies often follow a one-size-fits-all approach obtaining suboptimal outcomes for many patients who fail to experience response or recovery.
View Article and Find Full Text PDFIran J Basic Med Sci
January 2025
Department of Medical Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Objectives: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that have vital roles in activating further immune responses. However, due to their tumor-induced diversity, we decided to examine ILCs, T cells, and the associated cytokines in mouse models of breast cancer.
Materials And Methods: 4T1 and MC4-L2 cells were used to induce triple-negative and hormone-receptor-positive breast cancer, respectively.
Mol Ther Methods Clin Dev
March 2025
Immunologie-Oncologie, Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
CD4CD8 TCRαβ (double-negative [DN]) T cells represent a rare T cell population that promotes immunological tolerance through various cytotoxic mechanisms. In mice, autologous transfer of DN T cells has shown protective effects against autoimmune diabetes and graft-versus-host disease. Here, we characterized human DN T cells from people living with type 1 diabetes (PWT1D) and healthy controls.
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