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  • 1
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    Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-17
    Description: CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382081/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382081/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penaloza-MacMaster, Pablo -- Barber, Daniel L -- Wherry, E John -- Provine, Nicholas M -- Teigler, Jeffrey E -- Parenteau, Lily -- Blackmore, Stephen -- Borducchi, Erica N -- Larocca, Rafael A -- Yates, Kathleen B -- Shen, Hao -- Haining, W Nicholas -- Sommerstein, Rami -- Pinschewer, Daniel D -- Ahmed, Rafi -- Barouch, Dan H -- AI007245/AI/NIAID NIH HHS/ -- AI030048/AI/NIAID NIH HHS/ -- AI07387/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- AI096040/AI/NIAID NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI096040/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):278-82. doi: 10.1126/science.aaa2148.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. ; Department of Pathology and Immunology, WHO Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland. ; Department of Pathology and Immunology, WHO Collaborating Centre for Vaccine Immunology, University of Geneva, 1211 Geneva, Switzerland. Department of Biomedicine-Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland. ; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA. dbarouch@bidmc.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593185" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Animals ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Arenaviridae Infections/*immunology/virology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytokines/blood ; Epitopes, T-Lymphocyte/immunology ; Immune System Diseases/*etiology/immunology/pathology ; Immunologic Memory ; Inflammation/*etiology/immunology/pathology ; Lymphocytic choriomeningitis virus/*immunology/physiology ; Mice, Inbred C57BL ; Multiple Organ Failure/etiology ; Vaccination ; Viral Load ; Viral Vaccines/*adverse effects/*immunology ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Stable inhibitory activity of regulatory T cells requires the transcription factor Helios (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-17
    Description: The maintenance of immune homeostasis requires regulatory T cells (T(regs)). Given their intrinsic self-reactivity, T(regs) must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3(+) CD4 and Qa-1-restricted CD8 T(regs) results in defective regulatory activity and autoimmunity in mice. Helios-deficient T(regs) develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 T(regs) also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. The definition of Helios as a key transcription factor that stabilizes T(regs) in the face of inflammatory responses provides a genetic explanation for a core property of T(regs).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627635/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627635/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Hye-Jung -- Barnitz, R Anthony -- Kreslavsky, Taras -- Brown, Flavian D -- Moffett, Howell -- Lemieux, Madeleine E -- Kaygusuz, Yasemin -- Meissner, Torsten -- Holderried, Tobias A W -- Chan, Susan -- Kastner, Philippe -- Haining, W Nicholas -- Cantor, Harvey -- R01 AI037562/AI/NIAID NIH HHS/ -- R01AI37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):334-9. doi: 10.1126/science.aad0616.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. ; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. ; Bioinfo, Plantagenet, Canada. ; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Universite de Strasbourg, 67404 Illkirch, France. Faculte de Medecine, Universite de Strasbourg, Strasbourg, France. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. ; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA. harvey_cantor@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472910" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmunity/genetics/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; DNA-Binding Proteins/*biosynthesis/genetics ; Forkhead Transcription Factors/immunology ; Gene Expression ; Kidney/immunology ; Liver/immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pancreas/immunology ; STAT5 Transcription Factor/metabolism ; T-Lymphocytes, Regulatory/*immunology ; Transcription Factors/*biosynthesis/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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