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 allergic late-phase lung inflammation, BALB/c mice were injected intraperitoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then challenged intratracheally with the allergen. Late-phase allergic lung inflammation was defined by: (i) recruitment of eosinophils to airways, (ii) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in BAL fluids. The number of eosinophils recruited in allergic mice following intratracheal challenge with allergen was at least 300-fold higher P < or = 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 and C IV). 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 < or = 0.04). Moreover, IL-5 mRNA upregulation 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. Further, results from pulmonary function tests performed on the same allergic animals indicated that only animals from Test I and Test II groups had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell memory is required for the development of allergic asthma. That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid. Furthermore, if the Th2 cytokine profile was absent, then pulmonary functions remained normal.
Bell
S J
SJ
Section of Allergy/Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA. stephenb@boehringeringelheim.com
Metzger
W J
WJ
Welch
C A
CA
Gilmour
M I
MI
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002645:Chickens; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011058:Pollen / Q000276:immunology; D012129:Respiratory Function Tests; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D017931:DNA Primers; D007074:Immunoglobulin G; D007073:Immunoglobulin E