| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Wilson, Elizabeth B. Osokine, Ivan Brooks, David Yamada, Douglas H. Elsaesser, Heidi J. Cunningham, Cameron R. De La Torre, Juan Carlos Snell, Laura M. |
| Description |
Author Affiliation: Osokine I ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); Snell LM ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); Cunningham CR ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); Yamada DH ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); Wilson EB ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); Elsaesser HJ ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); de la Torre JC ( Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.); Brooks D ( Department of Microbiology, Immunology and Molecular Genetics andUCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095); |
| Abstract |
CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. Although the evolving immune environment during persistent infection reshapes established CD4 T-cell responses, the fate of naïve CD4 T cells primed in the midst of persistent infection is unclear. We demonstrate that, in marked contrast to the onset of infection, virus-specific CD4 T cells primed during an established persistent infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, virus-specific CD4 T cells primed during the established persistent infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established persistent virus infection. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
20 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Arenaviridae Infections Immunology CD4-Positive T-Lymphocytes Virology Gene Expression Regulation Interferon Type I Metabolism Th1 Cells Animals B-Lymphocytes Cell Differentiation Immunosuppression Lymphocytic Choriomeningitis Virus Mice Mice, Inbred C57BL Mice, Transgenic Receptors, Interferon Signal Transduction Tissue Distribution Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
