A ROLE FOR TH2 T-MEMORY CELLS IN EARLY AIRWAY-OBSTRUCTION

The role of T-cell memory in late-phase allergic lung inflammation is not well defined. To evaluate the role of systemic T-cell memory in al lergic late-phase lung inflammation, BALB/c mice were injected intrape ritoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then chall enged intratracheally with the allergen. Late-phase allergic lung infl ammation was defined by: (i) recruitment of eosinophils to airways, (i i) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in DAL fluids. The number of eosinophils re cruited in allergic mice following intratracheal challenge with allerg en was at least 300-fold higher P less than or equal to 0.01) in mice with allergen-specific T-memory cells in BAL fluid (Test I and Test II ) than in control mice without allergen-specific T-memory cells (C I a nd C nn. Further, the number of eosinophils recruited in Test I and II correlated with the magnitude of in vitro T-cell memory responses (r = 0.93, P less than or equal to 0.04). Moreover, IL-5 mRNA upregulatio n in BAL cells and Th2 cytokine production in BAL fluids were observed only in Test I and Test II, and not in any of the control groups. Fur ther, results from pulmonary function tests performed on the same alle rgic animals indicated that only animals from Test I and Test II group s had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell. m emory is required for the development of allergic asthma. That is, wit hout T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the ai rways, and no Th2 cytokine profile was detected in the BAL fluid. Furt hermore, if the Th2 cytokine profile was absent, then pulmonary functi ons remained normal. (C) 1996 Academic Press, Inc.