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

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-ty...

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Autores principales: Lei, Fengyang, Song, Jianyong, Haque, Rizwanul, Haque, Mohammad, Xiong, Xiaofang, Fang, Deyu, Croft, Michael, Song, Jianxun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731243/
https://www.ncbi.nlm.nih.gov/pubmed/23936461
http://dx.doi.org/10.1371/journal.pone.0070635
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author Lei, Fengyang
Song, Jianyong
Haque, Rizwanul
Haque, Mohammad
Xiong, Xiaofang
Fang, Deyu
Croft, Michael
Song, Jianxun
author_facet Lei, Fengyang
Song, Jianyong
Haque, Rizwanul
Haque, Mohammad
Xiong, Xiaofang
Fang, Deyu
Croft, Michael
Song, Jianxun
author_sort Lei, Fengyang
collection PubMed
description 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.
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spelling pubmed-37312432013-08-09 Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity Lei, Fengyang Song, Jianyong Haque, Rizwanul Haque, Mohammad Xiong, Xiaofang Fang, Deyu Croft, Michael Song, Jianxun PLoS One Research Article 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. Public Library of Science 2013-08-01 /pmc/articles/PMC3731243/ /pubmed/23936461 http://dx.doi.org/10.1371/journal.pone.0070635 Text en © 2013 Lei et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lei, Fengyang
Song, Jianyong
Haque, Rizwanul
Haque, Mohammad
Xiong, Xiaofang
Fang, Deyu
Croft, Michael
Song, Jianxun
Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title_full Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title_fullStr Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title_full_unstemmed Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title_short Regulation of A1 by OX40 Contributes to CD8(+) T Cell Survival and Anti-Tumor Activity
title_sort regulation of a1 by ox40 contributes to cd8(+) t cell survival and anti-tumor activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731243/
https://www.ncbi.nlm.nih.gov/pubmed/23936461
http://dx.doi.org/10.1371/journal.pone.0070635
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