Frontiers in Immunology (Dec 2013)

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

  • Markus eCornberg,
  • Markus eCornberg,
  • Laurie Lea Kenney,
  • Alex T Chen,
  • Sung-Kwon eKim,
  • Hans Peter Dienes,
  • Stephen eWaggoner,
  • Raymond M Welsh,
  • Liisa Kaarina Selin

DOI
https://doi.org/10.3389/fimmu.2013.00475
Journal volume & issue
Vol. 4

Abstract

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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.

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