ADOPTIVE TRANSFER OF ALLERGEN-SPECIFIC CD4(-CELLS INDUCES AIRWAY INFLAMMATION AND HYPERRESPONSIVENESS IN BROWN-NORWAY RATS() T)

Following allergen exposure, sensitized Brown-Norway rats develop airw ay hyperresponsiveness (AHR) and eosinophilic inflammation together wi th an increase in activated T cells (CD25(+)) in the airways. We teste d the hypothesis that CD4(+) T cells are involved directly in the acqu isition of AHR. Spleen T cells from animals that were injected intrape ritoneally 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 [H-3]thymidine uptake. For to tal T-cell transfer, spleen cells obtained from donor rats 4 days afte r 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 intravenous ly with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4(+) cell s, and 5 x 10(6) CD8(+) cells, and were exposed to ovalbumin aerosol 2 4 hr afterwards. After a further 24 hr, airway responsiveness to acety lcholine (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 calcula ted. Airway responsiveness was significantly increased in recipients o f sensitized total T cells compared with recipients of cells from sali ne-injected donor rats (P<0.05). There were significantly increased eo sinophil major basic protein (MBP)(+) cell counts/mm(2) in airway subm ucosal 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 f rom sensitized donors induced AHR in naive recipients (P<0.05), while sensitized CD8(+) and naive CD4(+) cells failed to do so. Our data ind icate that T cells may induce AHR through an eosinophilic airway infla mmation and that CD4(+) T cells may have a direct effect in this proce ss in Brown-Norway rats.