Peroxiredoxin II Regulates Effector and Secondary Memory CD8+ T Cell Responses |
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| Authors: | Ryan D. Michalek Katie E. Crump Ashley E. Weant Elizabeth M. Hiltbold Daniel G. Juneau Eun-Yi Moon Dae-Yeul Yu Leslie B. Poole Jason M. Grayson |
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| Affiliation: | aMetabolon Corporation, Durham, North Carolina, USA;bDepartment of Microbiology and Immunology;cDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;dDepartment of Bioscience and Biotechnology, Sejong University, Seoul, South Korea;eDisease Model Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea |
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| Abstract: | Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H2O2 on 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. |
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