RECOMBINANT INTERFERON-ALPHA SELECTIVELY INHIBITS THE PRODUCTION INTERLEUKIN-5 BY HUMAN CD4(-CELLS() T)

The effects of recombinant IFN-alpha on the production of IL-5 by huma n CD4(+) T cells were first analyzed on resting CD4(+) T cells purifie d from normal PBMC and stimulated either with a combination of PMA and anti-CD28 mAb or anti-CD3 mAb cross-linked on B7-1/CD32-transfected m ouse fibroblasts. We found that IFN-alpha profoundly inhibited in a do se-dependent manner IL-5 production by resting CD4(+) T cells whereas IL-10 was upregulated in both systems. The addition of a neutralizing anti-IL-10 mAb to PMA and anti-CD28 mAb upregulated IL-5 production by resting CD4(+) T cells but did not prevent IFN-alpha-induced IL-5 inh ibition. We then analyzed the effect of IFN-alpha on the production of cytokines by differentiated type 2 helper (Th2) CD4(+)CD3(-) cells is olated from peripheral blood of two patients with the hypereosinophili c syndrome. In both cases, IFN-alpha markedly inhibited IL-5 productio n while it induced mild upregulation of IL-4 and IL-10. Finally, the i nhibitory effect of IFN-alpha on IL-5 production was confirmed on a pa nel of Th2 and Th0 clones generated in vitro. In 2 out of 6 clones, IL -5 inhibition was associated with upregulation of IL-4 and IL-10, We c onclude that IFN-alpha selectively downregulates IL-5 synthesis by hum an CD4(+) T cells.