Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.

Autor: Buggert M; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Center for Infection Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden., Nguyen S; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., McLane LM; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., Steblyanko M; Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America., Anikeeva N; Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America., Paquin-Proulx D; Center for Infection Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America., Del Rio Estrada PM; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Ablanedo-Terrazas Y; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Noyan K; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Reuter MA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., Demers K; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., Sandberg JK; Center for Infection Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden., Eller MA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America., Streeck H; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America.; Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Jansson M; Department of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Nowak P; Center for Infection Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Sönnerborg A; Center for Infection Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Canaday DH; Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH, United States of America.; Geriatric Research, Education and Clinical Center, Louis Stokes VA Medical Center, Cleveland, OH, United States of America., Naji A; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., Wherry EJ; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America., Robb ML; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States of America., Deeks SG; Department of Medicine, University of California, San Francisco General Hospital, San Francisco, CA, United States of America., Reyes-Teran G; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Sykulev Y; Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America.; Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America., Karlsson AC; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Betts MR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2018 Apr 13; Vol. 14 (4), pp. e1006973. Date of Electronic Publication: 2018 Apr 13 (Print Publication: 2018).
DOI: 10.1371/journal.ppat.1006973
Abstrakt: 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.
Databáze: MEDLINE
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