Publication: Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses
Issued Date
2010-05-01
Resource Type
ISSN
15506606
00221767
00221767
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2-s2.0-77954477938
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Immunology. Vol.184, No.9 (2010), 4918-4925
Suggested Citation
Patcharee Ritprajak, Masaaki Hashiguchi, Fumihiko Tsushima, Narumon Chalermsarp, Miyuki Azuma Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses. Journal of Immunology. Vol.184, No.9 (2010), 4918-4925. doi:10.4049/jimmunol.0902478 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/29237
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Title
Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses
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Abstract
Keratinocytes (KCs) may play important roles for maintenance of peripheral tolerance in the upper layers of the skin. Coinhibitory signals mediated via the programmed death (PD)-1 and its ligand B7-H1 (PD-L1/CD274) are crucial for the downregulation of T cell immune responses and for the maintenance of peripheral tolerance. In this study, to investigate the role of KC-expressed B7-H1 in the regulation of T cell immune responses, we generated transgenic (tg) mice overexpressing B7-H1 under the control of keratin 14 (K14) promoter (K14-B7-H1 tg). K14-B7-H1 tg mice displayed impaired contact hypersensitivity (CH) responses to primary and secondary hapten challenges. The K14-B7-H1 tg mice did not exhibit substantial impairment of cutaneous dendritic cell migration after sensitization and of hapten-specific proliferation and IFN-γ production of CD4+ and CD8+ T cells in the draining lymph nodes, suggesting that overexpression of B7-H1 on KCs did not affect the induction phase of the CH response. The systemic or s.c. injection of hapten-sensitized T cells into the K14-B7-H1 tg mice did not efficiently induce the CH response. IFN-γ expression and apoptosis of KCs in the challenged ears were impaired in K14-B7-H1 tg mice. IFN-γ production by presensitized CD8+ T cells stimulated with hapten-pulsed KCs was markedly impaired for the KCs obtained from the K14-B7-H1 tg mice but was restored by the addition of an anti-B7-H1 mAb. These results suggest that KC-associated B7-H1 directly downregulates the effector function of CD8+ T cells by associating with PD-1 at local inflammatory sites and that it plays a role in peripheral T cell tolerance against exogenous Ags. Copyright © 2010 by The American Association of Immunologists, Inc.