Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses.
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| Abstract |
Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1(+)B7-DC(-)CD86(low), was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.
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| Authors | Fumihiko Tsushima, Hideyuki Iwai, Noriko Otsuki, Masaaki Abe, Sachiko Hirose, Tomohide Yamazaki, Hisaya Akiba, Hideo Yagita, Yuzo Takahashi, Ken Omura, Ko Okumura, Miyuki Azuma |
| Journal | European journal of immunology (Eur J Immunol) Vol. 33 Issue 10 Pg. 2773-82 (Oct 2003) ISSN: 0014-2980 [Print] Germany |
| PMID | 14515261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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