A critical role of IL-2 for the production and gene transcription of IL-5 in allergen-specific human T cell clones.
The role of IL-2 in IL-5 synthesis of human helper T cells was investigated. All of the Der f II (a major allergen of house dust mite)-specific T cell clones established from atopic asthmatic patients produced both IL-2 and IL-4 upon activation (Th0 phenotypes). Recombinant IL-2 induced gene expression and protein synthesis of IL-5 in T cell clones that produced IL-5 upon antigenic stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-2, indicating that the approximately 500 bp gene segment 5' upstream of the coding region was functionally sufficient for the gene transcription induced by IL-2. IL-2-induced IL-5 synthesis as well as proliferation was dependent on tyrosine kinases. Moreover, IL-5 production by T cell clones stimulated with immobilized anti-CD3 antibody was completely abrogated by anti-IL-2 neutralizing antibody, suggesting that IL-5 (a Th2 cytokine) synthesis of human helper T cells is dependent on IL-2 (a Th1 cytokine). Our present findings clearly demonstrated that IL-2, known as a T cell growth factor, exerts a cytokine promoting activity on T cells. IL-2 produced at the site of allergic inflammation might facilitate eosinophilic inflammation by inducing IL-5 production in T cells.
Mori
A
A
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Suko
M
M
Kaminuma
O
O
Nishizaki
Y
Y
Mikami
T
T
Ohmura
T
T
Hoshino
A
A
Inoue
S
S
Tsuruoka
N
N
Okumura
Y
Y
Sato
G
G
Ito
K
K
Okudaira
H
H
D000485:Allergens / Q000276:immunology; D039741:Antigens, Dermatophagoides; D002999:Clone Cells; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000819:agonists* / Q000096:biosynthesis* / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D007376:Interleukin-2; D015848:Interleukin-5