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Sökning: WFRF:(Paquin Proulx Dominic)

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1.
  • Buggert, Marcus, et al. (författare)
  • Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
  • 2018
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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2.
  • Pincikova, Terezia, et al. (författare)
  • Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells
  • 2018
  • Ingår i: Chest. - : ELSEVIER SCIENCE BV. - 0012-3692 .- 1931-3543. ; 153:5, s. E93-E96
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points. MAIT cells are a large, recently described subset of T cells that recognize microbial riboflavin metabolites presented by the highly evolutionarily conserved MR1 molecules. The MAIT cell deficiency was specific; other T-cell subsets were intact. Even though this is only one unique case, the findings lend significant support to the emerging role of MAIT cells in mucosal immune defense and suggest that MAIT cells may significantly modify the clinical phenotype of respiratory diseases.
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  • Resultat 1-2 av 2

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