IL-15 promotes cytokine production of human T helper cells.
IL-15 is a newly identified cytokine that has T cell and B cell growth factor activity similar to that of IL-2. In this study, a novel biologic function of IL-15 to promote cytokine production by human Th cells has been elucidated. Dermatophagoides farinae 11 (a major allergen of house dust mite)-specific human T cell clones produced IL-5 in response to recombinant human IL-15 as well as to either anti-CD3 or IL-2 stimulation. IL-5 mRNA became detectable 3 h after IL-15 stimulation and reached a maximum at 9 h. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-15, indicating that the approximately 500-bp human IL-5 promoter/enhancer segment 5' upstream of the coding region sufficiently responded to IL-15. IL-15-induced IL-5 synthesis was completely inhibited by the tyrosine kinase inhibitor, herbimycin A, suggesting the involvement of tyrosine kinases in the signal transduction leading to IL-5 synthesis as well as to proliferation of T cells induced by IL-15. Whereas IL-5 production by human peripheral T cells was abolished by the addition of anti-IL-2-neutralizing Abs into the culture, IL-15 restored the IL-5 synthesis despite effective IL-2 neutralization. IL-15 produced at the site of allergic inflammation may play a role in the recruitment and activation of eosinophils by inducing IL-5 (a Th2 cytokine) production by T cells.
Mori
A
A
Departments of Medicine, Faculty of Medicine, University of Tokyo, Japan.
Suko
M
M
Kaminuma
O
O
Inoue
S
S
Ohmura
T
T
Nishizaki
Y
Y
Nagahori
T
T
Asakura
Y
Y
Hoshino
A
A
Okumura
Y
Y
Sato
G
G
Ito
K
K
Okudaira
H
H
D000199:Actins / Q000235:genetics; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D016227:Benzoquinones; D002999:Clone Cells; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection
D000199:Actins; D000906:Antibodies; D016227:Benzoquinones; D017931:DNA Primers; D004791:Enzyme Inhibitors; D019409:Interleukin-15; D007376:Interleukin-2; D015848:Interleukin-5; D007378:Interleukins; D047029:Lactams, Macrocyclic; D011809:Quinones; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases