Title |
Clonal Exhaustion as a Mechanism to Protect Against Severe Immunopathology and Death from an Overwhelming CD8 T Cell Response
|
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Published in |
Frontiers in immunology, January 2013
|
DOI | 10.3389/fimmu.2013.00475 |
Pubmed ID | |
Authors |
Markus Cornberg, Laurie L. Kenney, Alex T. Chen, Stephen N. Waggoner, Sung-Kwon Kim, Hans P. Dienes, Raymond M. Welsh, Liisa K. Selin |
Abstract |
The balance between protective immunity and immunopathology often determines the fate of the virus-infected host. How rapidly virus is cleared is a function of initial viral load, viral replication rate, and efficiency of the immune response. Here, we demonstrate, with three different inocula of lymphocytic choriomeningitis virus (LCMV), how the race between virus replication and T cell responses can result in different disease outcomes. A low dose of LCMV generated efficient CD8 T effector cells, which cleared the virus with minimal lung and liver pathology. A high dose of LCMV resulted in clonal exhaustion of T cell responses, viral persistence, and little immunopathology. An intermediate dose only partially exhausted the T cell responses and resulted in significant mortality, and the surviving mice developed viral persistence and massive immunopathology, including necrosis of the lungs and liver. This suggests that for non-cytopathic viruses like LCMV, hepatitis C virus, and hepatitis B virus, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Switzerland | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 4 | 4% |
Germany | 1 | <1% |
Unknown | 101 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 24 | 23% |
Researcher | 19 | 18% |
Student > Bachelor | 11 | 10% |
Student > Doctoral Student | 10 | 9% |
Student > Master | 6 | 6% |
Other | 8 | 8% |
Unknown | 28 | 26% |
Readers by discipline | Count | As % |
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Immunology and Microbiology | 34 | 32% |
Agricultural and Biological Sciences | 16 | 15% |
Medicine and Dentistry | 13 | 12% |
Biochemistry, Genetics and Molecular Biology | 11 | 10% |
Computer Science | 1 | <1% |
Other | 3 | 3% |
Unknown | 28 | 26% |