Background: We have recently demonstrated that allergic eosinophilic inflammation is transferred to unprimed mice by infusing IL-5-producing CD4+ T cells. The contribution of mast cells to the development of eosinophilic inflammation is controversial. Methods: To clarify the possible different roles of CD4+ T cells and mast cells in eosinophilic inflammation, we compared antigen-induced airway eosinophilia between mast-cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1-+/+). Results: The time course study indicated that equivalent numbers of eosinophils were recruited into the airway of both +/+ and W/Wv mice 6, 24, 96, and 216 h after antigen challenge, whereas the number of eosinophils 48 h after antigen challenge was significantly lower in W/Wv compared to +/+ mice. Administration of either anti-CD4 or anti-IL-5 monoclonal antibody almost completely inhibited antigen-induced eosinophil recruitment in W/Wv mice 48 h after antigen challenge. In contrast, the inhibitory effect of these antibodies in +/+ mice were partial (∼50% inhibition). Anti-CD4 and anti-IL-5 antibodies equally suppressed airway eosinophilia in both +/+ and W/Wv mice 96 h after antigen challenge. Conclusion: Our study indicates that CD4+ T cells are crucially involved in the development of allergic eosinophilic inflammation, while mast cells may play a supplemental role depending on the kinetics of the response.

1.
Corrigan CJ, Kay AB: T cells and eosinophils in the pathogenesis of asthma. Immunol Today 1992;13:501–507.
2.
Kay AB, ‘Helper’ (CD4+) T cells and eosinophils in allergy and asthma. Am Rev Respir Dis 1992;145:S22–S26.
3.
Mori A, Suko M, Nishizaki Y, Kaminuma O, Kobayashi S, Matsuzaki G, Yamamoto K, Ito K, Tsuruoka N, Okudaira H: IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and immunosuppressants FK506 and cyclosporin A. Int Immunol 1995;7:449–457.
4.
Mori A, Kaminuma O, Suko M, Mikami T, Nishizaki Y, Ohmura T, Hoshino A, Asakura Y, Miyazawa K, Ando T, Okumura Y, Yamamoto K, Okudaira H: Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases: A study with allergen-specific human helper T cells. J Allergy Clin Immunol 1997;100:S56–64.
5.
Nakajima H, Iwamoto I, Tomoe S, Matsumura R, Tomioka H, Takatsu K, Yoshida S: CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis 1992;146:374–377.
6.
Gavett SH, Chen X, Finkelman F, Wills-Karp M: Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol 1994;10:587–593.
7.
Kaminuma O, Mori A, Ogawa K, Nakata A, Kikkawa H, Naito K, Suko M, Okudaira H: Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones. Am J Respir Cell Mol Biol 1997;16:448–454.
8.
Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, Paul WE: Mast cell lines produce lymphokines in response to cross-linkage of Fcσ RI or to calcium ionophores. Nature 1989;339:64–67.
9.
Okayama Y, Petit-Frere C, Kassel O, Semper A, Quint D, Tunon-de-Lara MJ, Bradding P, Holgate ST, Church MK: IgE-dependent expression of mRNA for IL-4 and IL-5 in human lung mast cells. J Immunol 1995;155:1796–1808.
10.
Levi-Schaffer F, Temkin V, Malamud V, Feld S, Zilberman Y: Mast cells enhance eosinophil survival in vitro: Role of TNF-α and granulocyte-macrophage colony-stimulating factor. J Immunol 1998;160:5554–5562.
11.
Brusselle GG, Kips JC, Tavernier JH, van der Heyden JG, Cuvelier CA, Pauwels RA, Bluethmann H: Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 1994;24:73–80.
12.
Takeda K, Hamelmann E, Joetham A, Shultz LD, Larsen GL, Irvin CG, Gelfand EW: Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J Exp Med 1997;186:449–454.
13.
Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG: Interleukin-5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 1996;183:195–201.
14.
Renzetti LM, Paciorek PM, Tannu SA, Rinaldi NC, Tocker JE, Wasserman MA, Gater PR: Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airway. J Pharmacol Exp Ther 1996;278:847–853.
15.
Foster A, Chan CC: Peptide leukotriene involvement in pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig. Int Arch Allergy Appl Immunol 1991;96:279–284.
16.
Itoh K, Takahashi E, Mukaiyama O, Satoh Y, Yamaguchi T: Effects of thromboxane synthase inhibitor (CS-518) on the eosinophil-dependent late asthmatic response and airway hyperresponsiveness in guinea pigs. Int Arch Allergy Immunol 1996;109:79–85.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.