Sh. Gavett et al., DEPLETION OF MURINE CD4-LYMPHOCYTES PREVENTS ANTIGEN-INDUCED AIRWAY HYPERREACTIVITY AND PULMONARY EOSINOPHILIA( T), American journal of respiratory cell and molecular biology, 10(6), 1994, pp. 587-593
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.