Signals mediated by chemokine receptors may compete with T cell receptor stop signals and determine the duration of T cell-antigen-presenting cell interactions. Here we show that during T cell stimulation by antigen-presenting cells, T cell chemokine receptors coupled to G(q) and/or G(11) protein were recruited to the immunological synapse by a G(i)-independent mechanism. When chemokine receptors were sequestered at the immunological synapse, T cells became insensitive to chemotactic gradients, formed more stable conjugates and finally responded with enhanced proliferation and cytokine production. We suggest that chemokine receptor trapping at the immunological synapse enhances T cell activation by improving T cell-antigen-presenting cell attraction and impeding the 'distraction' of successfully engaged T cells by other chemokine sources.
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http://dx.doi.org/10.1038/ni1191 | DOI Listing |
Arch Endocrinol Metab
January 2025
Instituto Nacional de Ciência e Tecnologia para Avaliação de Tecnologias em Saúde Hospital de Clínicas de Porto Alegre Porto AlegreRS Brasil Instituto Nacional de Ciência e Tecnologia para Avaliação de Tecnologias em Saúde (IATS) - CNPq/Brasil, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil.
Objective: To determine circulating endothelial progenitor cells (EPC) counts and levels of inflammatory markers in individuals with and without type 1 diabetes mellitus (T1DM) in response to an intense aerobic exercise session.
Subjects And Methods: In total, 15 adult men with T1DM and 15 healthy individuals underwent a 30-minute aerobic exercise session on a cycle ergometer at 60% of the peak heart rate. The EPC count (CD45/CD34/KDR), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were measured before and 60 minutes after the session.
Breast Cancer Res
January 2025
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Background: CDK4/6 inhibitors have significantly improved the survival of patients with HR-positive/HER2-negative breast cancer, becoming a first-line treatment option. However, the development of resistance to these inhibitors is inevitable. To address this challenge, novel strategies are required to overcome resistance, necessitating a deeper understanding of its mechanisms.
View Article and Find Full Text PDFFront 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.
View Article and Find Full Text PDFJ Pathol Clin Res
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
CXC chemokine receptor 4 (CXCR4) and programmed cell death-ligand 1 (PD-L1) are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer (GC) remain unknown. Moreover, the correlation between their expression levels in GC remains elusive.
View Article and Find Full Text PDFFront Immunol
January 2025
Laboratorio de Pediatria Clinica (LIM36), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Introduction: Chemokines and their receptors are essential for leukocyte migration to several tissues, including human milk. Here, we evaluated the homing of T and B lymphocyte subsets to breast milk in response to ongoing respiratory infections in the nursing infant.
Methods: Blood and mature milk were collected from healthy mothers of nurslings with respiratory infections (Group I) and from healthy mothers of healthy nurslings (Group C).
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