Clonal exhaustion as a mechanism to protect against severe immunopathology and death from an overwhelming CD8 T cell response.

Frontiers in Immunology

Markus eCornberg¹  Hans Peter Dienes²  Alex T Chen³  Raymond M Welsh³  Stephen eWaggoner³  Sung-Kwon eKim³  Liisa Kaarina Selin³  Laurie Lea Kenney³ 

[1] Hannover Medical School;Medical University of Vienna;University of Massachusetts Medical School;

关键词: Liver;    Lung;    T cells;    lcmv;    CD8;    immunopathology;   

DOI  :  10.3389/fimmu.2013.00475

来源: DOAJ

【 摘 要 】

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 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, HCV and HBV, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death.

【 授权许可】

Unknown