DEPLETION OF MURINE CD4-LYMPHOCYTES PREVENTS ANTIGEN-INDUCED AIRWAY HYPERREACTIVITY AND PULMONARY EOSINOPHILIA( T)

The pathogenesis of asthma remains unclear. An in vivo murine model of antigen-induced airway hyperreactivity and inflammation was developed to investigate the possibility, suggested by a wealth of descriptive human data, that alterations in immunoregulation are important in the genesis of airway hyperreactivity. A/J mice developed airway hyperreac tivity and markedly increased numbers of pulmonary inflammatory cells following intraperitoneal sensitization and intratracheal challenge wi th sheep red blood cells. Notably, eosinophils were a prominent compon ent of the inflammatory infiltrate. The dependence of these phenomena, both pathologic and functional, on CD4+ T lymphocytes was investigate d by in vivo depletion of CD4+ cells using the anti-CD4 mAb GK1.5. Whe n administered before antigen challenge, GK1.5 completely prevented bo th airway hyperreactivity and the infiltration of eosinophils. This mo del provides the first direct demonstration of the dependence of airwa y hyperreactivity upon CD4+ T lymphocytes, and the results are consist ent with the possibility that eosinophils are effectors of this respon se.