Peroxiredoxin II Regulates Effector and Secondary Memory CD8+ T cell Responses

Authors

• Ryan D. Michalek, Metabolon Corporation
• Katie E. Crump, Wake Forest University School of MedicineFollow
• Ashley E. Weant, Wake Forest University School of Medicine
• Elizabeth M. Hiltbold, Wake Forest University School of Medicine
• Daniel G. Juneau, Wake Forest University School of Medicine
• Eun-Yi Moon, Sejong University
• Dae-Yeul Yu, Korea Research Institute of Bioscience and Biotechnology
• Leslie B. Poole, Wake Forest University School of Medicine
• Jason M. Grayson, Wake Forest University School of Medicine

Document Type

Article

Publication Title

Journal of Virology

ISSN

0022-538X

Publication Date

12-2012

Abstract

Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H₂O₂on an antigen-specific CD8⁺ T cell response was unknown. Following T cell receptor (TCR) stimulation, the expression and oxidation of peroxiredoxin II (PrdxII), a critical antioxidant enzyme, increased in CD8⁺ T cells. Deletion of PrdxII increased ROI, S phase entry, division, and death during in vitro division. During primary acute viral and bacterial infection, the number of effector CD8⁺ T cells in PrdxII-deficient mice was increased, while the number of memory cells were similar to those of the wild-type cells. Adoptive transfer of P14 TCR transgenic cells demonstrated that the increased expansion of effector cells was T cell autonomous. After rechallenge, effector CD8⁺ T cells in mutant animals were more skewed to memory phenotype than cells from wild-type mice, resulting in a larger secondary memory CD8⁺ T cell pool. During chronic viral infection, increased antigen-specific CD8⁺ T cells accumulated in the spleens of PrdxII mutant mice, causing mortality. These results demonstrate that PrdxII controls effector CD8⁺ T cell expansion, secondary memory generation, and immunopathology.

DOI

10.1128/JVI.01559-12

Volume

86

Issue

24

First Page

13629

Last Page

13641

NSUWorks Citation

Michalek, Ryan D.; Katie E. Crump; Ashley E. Weant; Elizabeth M. Hiltbold; Daniel G. Juneau; Eun-Yi Moon; Dae-Yeul Yu; Leslie B. Poole; and Jason M. Grayson. 2012. "Peroxiredoxin II Regulates Effector and Secondary Memory CD8+ T cell Responses." Journal of Virology 86, (24): 13629-13641. doi:10.1128/JVI.01559-12.