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Adoptive transfer of allergen‐specific CD4 + T cells induces airway inflammation and hyperresponsiveness in Brown–Norway rats
Author(s) -
HACZKU A.,
MACARY P.,
HUANG T.J.,
TSUKAGOSHI H.,
BARNES P. J.,
KAY A. B.,
KEMENY D. M.,
CHUNG K. F.,
MOQBEL R.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.d01-2221.x
Subject(s) - ovalbumin , eosinophil , splenocyte , spleen , immunology , sensitization , chemistry , cd8 , adoptive cell transfer , endocrinology , t cell , medicine , allergen , methacholine , microbiology and biotechnology , lung , antigen , biology , immune system , allergy , asthma , respiratory disease
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 vitr o to ovalbumin, but not to bovine serum albumin, as measured by []> 3 H]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 50×10 6 total T cells, 20×10 6 and 5×10 6 CD4 + cells, and 5×10 6 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 (PC 100 , PC 200 andPC 300 ) (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/mm 2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP + cells and PC 100 ( 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.