GLUCOCORTICOSTEROIDS AFFECT FUNCTIONS OF AIRWAY-DERIVED AND BLOOD-DERIVED HUMAN T-CELL CLONES, FAVORING THE TH1 PROFILE THROUGH 2 MECHANISMS

Glucocorticosteroids (GCS) are beneficial in allergic asthma. GCS ther apy results in reduced mRNA expression of interleukin-4 (IL-4) and IL- 5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. In vitro studies with blood-derived T cells, however, show inhibition of all three cytokines by GCS. We studied the effects of GCS on T cells f rom BAL in vitro, namely Th0-, Th1-, and Th2-like clones; and we compa red BAL- with blood-derived clones. Dexamethasone (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5, and IFN-gamma in all 20 clo nes tested. IFN-gamma production was inhibited significantly less than IL-4 and IL-5. DEX enhanced the ratio IFN-gamma/IL-4 (mean +/- SEM: c ontrol, 28.7 +/- 17.6; with 10(-7) M DEX, 55.0 +/- 27.5, P < 0.005). I nterestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and prol iferation; 1) In low IL-2. producers DEX blocked IL-2 production and d ecreased IL-2R alpha expression and proliferation; 2) In high IL-2 pro ducers DEX inhibited IL-2 production partially and enhanced IL-2R alph a expression and proliferation. Anti-IL-2 and anti-IL-2R alpha blocked the DEX-induced increase in proliferation. High levels of added IL-2 induced the second type of response. In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by DEX than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patient s with asthma. The differential effects of DEX on the proliferation of high and low IL-2 producers in vitro may implicate a selective outgro wth of Th1-like T cells in vivo in patients treated with steroids.