Recombinant interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells.
The effects of recombinant IFN-alpha on the production of IL-5 by human CD4+ T cells were first analyzed on resting CD4+ T cells purified 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 mouse fibroblasts. We found that IFN-alpha profoundly inhibited in a dose-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 inhibition. We then analyzed the effect of IFN-alpha on the production of cytokines by differentiated type 2 helper (Th2) CD4+CD3- cells isolated from peripheral blood of two patients with the hypereosinophilic syndrome. In both cases, IFN-alpha markedly inhibited IL-5 production while it induced mild upregulation of IL-4 and IL-10. Finally, the inhibitory effect of IFN-alpha on IL-5 production was confirmed on a panel 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 conclude that IFN-alpha selectively downregulates IL-5 synthesis by human CD4+ T cells.
Schandené
L
L
Department of Immunology, Hôpital Erasme-Cliniques Universitaires de Bruxelles, Belgium.
Del Prete
G F
GF
Cogan
E
E
Stordeur
P
P
Crusiaux
A
A
Kennes
B
B
Romagnani
S
S
Goldman
M
M
D000818:Animals; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000276:immunology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D018418:Th2 Cells / Q000378:metabolism*; D014162:Transfection
D018106:CD28 Antigens; D017931:DNA Primers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015848:Interleukin-5; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4