B7-H5 costimulates human T cells via CD28H

Yuwen Zhu; Sheng Yao; Bettina P. Iliopoulou; Xue Han; Mathew M. Augustine; Haiying Xu; Ryan T. Phennicie; Sarah J. Flies; Megan Broadwater; William Ruff; Janis M. Taube; Linghua Zheng; Liqun Luo; Gefeng Zhu; Jianzhu Chen; Lieping Chen

doi:10.1038/ncomms3043

B7-H5 costimulates human T cells via CD28H

Yuwen Zhu, Sheng Yao, Bettina P. Iliopoulou, Xue Han, Mathew M. Augustine, Haiying Xu, Ryan T. Phennicie, Sarah J. Flies, Megan Broadwater, William Ruff, Janis M. Taube, Linghua Zheng, Liqun Luo, Gefeng Zhu, Jianzhu Chen, Lieping Chen

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

Abstract

The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.

Original language	English (US)
Article number	2043
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3043
State	Published - 2013

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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@article{76809c6c23cf4f6e912cbcc0062665a4,

title = "B7-H5 costimulates human T cells via CD28H",

abstract = "The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.",

author = "Yuwen Zhu and Sheng Yao and Iliopoulou, {Bettina P.} and Xue Han and Augustine, {Mathew M.} and Haiying Xu and Phennicie, {Ryan T.} and Flies, {Sarah J.} and Megan Broadwater and William Ruff and Taube, {Janis M.} and Linghua Zheng and Liqun Luo and Gefeng Zhu and Jianzhu Chen and Lieping Chen",

note = "Funding Information: We thank Dr Xiaobo Wang at Johns Hopkins University for technical assistance, and Beth Cadugan for editing the manuscript. This work was partially supported by US National Institutes of Health (NIH) grants CA98721, CA113341 and AI72592.",

year = "2013",

doi = "10.1038/ncomms3043",

language = "English (US)",

volume = "4",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - B7-H5 costimulates human T cells via CD28H

AU - Zhu, Yuwen

AU - Yao, Sheng

AU - Iliopoulou, Bettina P.

AU - Han, Xue

AU - Augustine, Mathew M.

AU - Xu, Haiying

AU - Phennicie, Ryan T.

AU - Flies, Sarah J.

AU - Broadwater, Megan

AU - Ruff, William

AU - Taube, Janis M.

AU - Zheng, Linghua

AU - Luo, Liqun

AU - Zhu, Gefeng

AU - Chen, Jianzhu

AU - Chen, Lieping

N1 - Funding Information: We thank Dr Xiaobo Wang at Johns Hopkins University for technical assistance, and Beth Cadugan for editing the manuscript. This work was partially supported by US National Institutes of Health (NIH) grants CA98721, CA113341 and AI72592.

PY - 2013

Y1 - 2013

N2 - The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.

AB - The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.

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JO - Nature communications

JF - Nature communications

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ER -

B7-H5 costimulates human T cells via CD28H

Abstract

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