Regulation of A1 by OX40 Contributes to CD8+ T Cell Survival and Anti-Tumor Activity

Fengyang Lei, Jianyong Song, Rizwanul Haque, Mohammad Haque, Xiaofang Xiong, Deyu Fang, Michael Croft, Jianxun Song

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Abstract

The TNFR family member OX40 (CD134) is critical for optimal clonal expansion and survival of T cells. However, the intracellular targets of OX40 in CD8 T cells are not fully understood. Here we show that A1, a Bcl-2 family protein, is regulated by OX40 in effector CD8 T cells. In contrast to wild-type T cells, OX40-deficient CD8 T cells failed to maintain A1 expression driven by antigen. Conversely, enforced OX40 stimulation promoted A1 expression. In both situations, the expression of A1 directly correlated with CD8 T cell survival. In addition, exogenous expression of A1 in OX40-deficient CD8 T cells reversed their survival defect in vitro and in vivo. Moreover, forced expression of A1 in CD8 T cells from OX40-deficient mice restored the ability of these T cells to suppress tumor growth in a murine model. These results indicate that OX40 signals regulate CD8 T cell survival at least in part through maintaining expression of the anti-apoptotic molecule A1, and provide new insight into the mechanism by which OX40 may impact anti-tumor immunity.

Original languageEnglish (US)
Article numbere70635
JournalPloS one
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2013

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Lei, F., Song, J., Haque, R., Haque, M., Xiong, X., Fang, D., Croft, M., & Song, J. (2013). Regulation of A1 by OX40 Contributes to CD8+ T Cell Survival and Anti-Tumor Activity. PloS one, 8(8), [e70635]. https://doi.org/10.1371/journal.pone.0070635