Peroxiredoxin II regulates effector and secondary memory CD8+ T cell responses.
Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H(2)O(2) 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.
Metabolon Corporation, Durham, North Carolina, USA.
Ryan D
RD
Michalek
Katie E
KE
Crump
Ashley E
AE
Weant
Elizabeth M
EM
Hiltbold
Daniel G
DG
Juneau
Eun-Yi
EY
Moon
Dae-Yeul
DY
Yu
Leslie B
LB
Poole
Jason M
JM
Grayson
D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
D054464:Peroxiredoxins