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The Journal of Immunology, 2007, 178, 6058 -6065
Copyright © 2007 by The American Association of Immunologists, Inc.

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*Substance via MeSH

Nasal Cholera Toxin Elicits IL-5 and IL-5 Receptor {alpha}-Chain Expressing B-1a B Cells for Innate Mucosal IgA Antibody Responses1

Kosuke Kataoka*,{dagger}, Keiko Fujihashi*, Shinichi Sekine*, Tatsuya Fukuiwa*,{ddagger}, Ryoki Kobayashi*, Hideaki Suzuki*,§, Hideki Nagata{dagger}, Kiyoshi Takatsu, Satoshi Shizukuishi{dagger}, Jerry R. McGhee* and Kohtaro Fujihashi2,*

* Departments of Pediatric Dentistry and Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294; {dagger} Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Osaka, Japan; {ddagger} Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; § Department of Dental Caries Control and Aesthetic Dentistry, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan; and Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Sciences, University of Tokyo, Tokyo, Japan

In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. High numbers of TNP-specific IgA Ab-forming cells were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs), and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. Flow cytometric analysis showed that higher numbers of surface IgA+, CD5+ B cells (B-1a B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone. Furthermore, increased levels of IL-5R {alpha}-chain were expressed by B-1a B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus, CD4+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 mAb, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell-independent Ag due to the cross-talk between IL-5R{alpha}+ B-1a B cells and IL-5-producing CD4+ T cells in the mucosal effector lymphoid tissues.

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 is supported by National Institutes of Health Grants DE 12242, AI 43197, AI 18958, and AG 025873, as well as by Grants-in-Aid C17592179 and A17209066 from the Ministry of Education, Science, Sports, and Culture of Japan.

2 Address correspondence and reprint requests to Dr. Kohtaro Fujihashi, Departments of Pediatric Dentistry and Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, 845 19th Street South BBRB 761, Birmingham, AL 35294. E-mail address: kohtarof{at}uab.edu

3 Abbreviations used in this paper: nCT, native cholera toxin; AFC, Ab-forming cell; DC, dendritic cell; IL-5R{alpha}, IL-5R {alpha}-chain; mCT, mutant CT; NP, nasal passage; NW, nasal wash; S-IgA, secretory IgA; sIgA, surface IgA; SMG, submandibular gland; TI Ag, T cell-independent Ag; TNP-LPS, trinitrophenyl-LPS.




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