Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in Brown-Norway rats

Angela Franciska Haczku, P. Macary, T. J. Huang, H. Tsukagoshi, P. J. Barnes, A. B. Kay, D. M. Kemeny, K. F. Chung, R. Moqbel

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61 Scopus citations

Abstract

Following allergen exposure, sensitized Brown Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 106 total T cells, 20 x 106 and 5 x 106 CD4+ cells, and 5 x 106 CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr. airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values (PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P < 0.05). There were significantly increased eosinophil major basic protein (MBP)+ cell counts/mm2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP+ cells and PC100 (r = 0.75; P < 0.03) in recipients of sensitized total T cells. Purified CD4+ T cells from sensitized donors induced AHR in naive recipients (P < 0.05), while sensitized CD8+ and naive CD4+ cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4+ T cells may have a direct effect in this process in Brown-Norway rats.

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalImmunology
Volume91
Issue number2
StatePublished - 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Haczku, A. F., Macary, P., Huang, T. J., Tsukagoshi, H., Barnes, P. J., Kay, A. B., Kemeny, D. M., Chung, K. F., & Moqbel, R. (1997). Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in Brown-Norway rats. Immunology, 91(2), 176-185.