Naive T lymphocytes traffic through the organism in search for antigen, alternating between blood and secondary lymphoid organs. Lymphocyte homing to lymph nodes relies on CCL21 chemokine sensing by CCR7 receptors, while exit into efferent lymphatics relies on sphingolipid S1P sensing by S1PR1 receptors. While both molecules are claimed chemotactic, a quantitative analysis of naive T lymphocyte migration along defined gradients is missing. Here, we used a reductionist approach to study the real-time single-cell response of naive T lymphocytes to CCL21 and serum rich in bioactive S1P. Using microfluidic and micropatterning ad hoc tools, we show that CCL21 triggers stable polarization and long-range chemotaxis of cells, whereas S1P-rich serum triggers a transient polarization only and no significant displacement, potentially representing a brief transmigration step through exit portals. Our data thus suggest that naive T lymphocyte chemotax long distances to CCL21 but not toward a source of bioactive S1P.
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http://dx.doi.org/10.1016/j.isci.2023.107695 | DOI Listing |
Turk Arch Pediatr
January 2025
Division of Allergy and Immunology, Department of Pediatrics, Marmara University Faculty of Medicine, İstanbul, Türkiye.
Objective: Prolidase deficiency is a metabolic and immunological disorder that is inherited in an autosomal recessive manner. In prolidase deficiency, a broad spectrum of differences is observed in patients, ranging from asymptomatic to multisystem involvement. There is scarce information in the literature on the atypical features and immunophenotypes of this disease.
View Article and Find Full Text PDFUnlabelled: SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role.
View Article and Find Full Text PDFESMO Open
January 2025
Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy.
Background: Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.
Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies.
View Article and Find Full Text PDFEur J Case Rep Intern Med
December 2024
Clínica de Medicina, Serviço de Medicina Interna, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
Unlabelled: Sarcoidosis is a multisystemic syndrome characterized by non-caseous granulomatous inflammation, although necrotizing sarcoid granulomatosis is considered part of the spectrum of the disease. Drug induced sarcoidosis-like reaction (DISR) is a systemic granulomatous reaction, which is histopathologically identical to primary sarcoidosis - mostly described after the use of biologics like tumour necrosis factor alpha antagonists but also anti-CD20 (rituximab). The authors present the very rare case of a woman with a primary Sjögren's syndrome (pSS) started on rituximab for disease control, which evolved with a 3-year indolent progressive systemic sarcoid reaction.
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