Increased levels of IL-4 in CD8(+) T cells in atopic asthma

Background: In view of reports that CD8(+) T cells may produce T-H2-type cytokines and our own finding that levels of intracellular IL-4 are higher in CD8(+) than CD4(+) T cells in healthy nonatopic subjects, we have hypothesized that the capacity of CD8(+) T cells to produce IL-4 may be increased in atopic asthma, a disease characterized by high production of T-H2 cytokines. Methods: Levels of IL-4 and interferon-gamma were measured by ELISA in cell lysates and in 20- and 48-hour cultures of concanavalin A-stimulated purified peripheral blood CD8(+) T cells in seven patients with mild atopic asthma and seven healthy nonatopic subjects. Results: Resting CD8(+) T cells in patients with asthma contained significantly more IL-4 than those of healthy nonatopic subjects (median, 26 pg/10(6) cells; range, 17 to 84 pg/10(6) cells vs 16 pg/10(6) cells; 10 to 28 pg/10(6) cells), with no difference in intracellular interferon-gamma levels. In the healthy control subjects, but not in the patients with asthma, levels of intracellular IL-4 correlated negatively,vith levels of interferon-gamma in resting CD8(+) T cells (r(s) = -0.9411, p = 0.005). Stimulation with concanavalin A produced a consistent and significant increase in secretion of interferon-gamma, but not IL-4, with no difference between the two groups of subjects. Conclusion: The results of this study suggest that CD8(+) T cells from patients with asthma may be an important source of the T-H2-type cytokine IL-4. This capacity appears to be acquired in vivo, possibly by conditioning by IL-4 produced in the inflamed airways.