HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nagashima, O. Articles by Akiba, H. Search for Related Content PubMed PubMed Citation Articles by Nagashima, O. Articles by Akiba, H.

B7-H3 Contributes to the Development of Pathogenic Th2 Cells in a Murine Model of Asthma¹

Osamu Nagashima^2,*,,, Norihiro Harada^2,*,,, Yoshihiko Usui^*,, Tomohide Yamazaki^*, Hideo Yagita^*, Ko Okumura^*, Kazuhisa Takahashi^, and Hisaya Akiba^3,*

^* Department of Immunology, Department of Respiratory Medicine, and Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, and Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan

B7-H3 is a new member of the B7 family. The receptor for B7-H3 has not been identified, but it seems to be expressed on activated T cells. Initial studies have shown that B7-H3 provides a stimulatory signal to T cells. However, recent studies suggest a negative regulatory role for B7-H3 in T cell responses. Thus, the immunological function of B7-H3 is controversial and unclear. In this study, we investigated the effects of neutralizing anti-B7-H3 mAb in a mouse model of allergic asthma to determine whether B7-H3 contributes to the development of pathogenic Th2 cells and pulmonary inflammation. Administration of anti-B7-H3 mAb significantly reduced airway hyperreactivity with a concomitant decrease in eosinophils in the lung as compared with control IgG-treated mice. Treatment with anti-B7-H3 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the draining lymph node cells. Although blockade of B7-H3 during the induction phase abrogated the development of asthmatic responses, B7-H3 blockade during the effector phase did not inhibit asthmatic responses. These results indicated an important role for B7-H3 in the development of pathogenic Th2 cells during the induction phase in a murine model of asthma.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

² O.N. and N.H. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Hisaya Akiba, Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail address: hisaya{at}med.juntendo.ac.jp

⁴ Abbreviations used in this paper: AHR, airway hyperreactivity; AB, Alcian blue; BALF, bronchoalveolar lavage fluid; BMDC, bone marrow-derived dendritic cell; BMMacs, bone marrow-derived macrophages; DC, dendritic cell; LN, lymph node; PAS, periodic acid-Schiff; Penh, enhanced pause; rmB7-H3, mouse rB7-H3.