Department of Pathology
Immunity | Immunopathology
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.
CD8, LCMV, T cells, clonal exhaustion, immunopathology, liver, lung
Rights and Permissions
Copyright: © 2013 Cornberg, Kenney, Chen, Waggoner, Kim, Dienes, Welsh and Selin.
DOI of Published Version
Front Immunol. 2013 Dec 20;4:475. doi: 10.3389/fimmu.2013.00475. eCollection 2013. Link to article on publisher's site
Frontiers in immunology
Cornberg M, Kenney LL, Chen AT, Waggoner SN, Kim S, Dienes HP, Welsh RM, Selin LK. (2013). Clonal exhaustion as a mechanism to protect against severe immunopathology and death from an overwhelming CD8 T cell response. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.3389/fimmu.2013.00475. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/2042