IL-2-induced IL-9 production by allergen-specific human helper T-cell clones.
BACKGROUND
IL-9 is an important cytokine in allergic diseases such as asthma, atopic dermatitis, etc. T helper (Th) cells seem to be the main source of IL-9. Cellular and molecular mechanisms of IL-9 production by human Th cells have been poorly understood.


METHODS
Dermatophagoides farinae(Der f)-specific Th clones were established from peripheral blood lymphocytes of atopic asthmatics, and cytokine synthesis in response to various stimuli was determined by specific ELISAs.


RESULTS
IL-9 was produced by 14 of 27 human Th clones upon T cell receptor (TCR) stimulation, immobilized anti-CD3 antibody (Ab). IL-9 production was significantly enhanced by the addition of anti-CD28 Ab into the culture, indicating the role of costimulatory signal on IL-9 synthesis. Pharmacologically, IL-9 production was induced by ionomycin (IOM) alone, and enhanced by phorbol 12-myristate 13-acetate (PMA). rIL-2 induced IL-9 production by 8 out of 19 Th clones. IL-9 production by Th clones stimulated with immobilized anti-CD3 Ab was significantly suppressed by the addition of anti-IL-2 neutralizing Ab into the culture.


CONCLUSIONS
Approximately half of the Der f-specific Th clones derived from atopic asthmatics produced IL-9 upon TCR stimulation. Ca(2+) signal, CD28 signal, and IL-2 receptor signal seem to play important roles in IL-9 production by human Th cells. Moreover, synthesis of IL-9, a Th2 cytokine, is dependent on IL-2, a Th1 cytokine, which is produced by Th cells themselves.
Kajiyama
Yuichiro
Y
National Hospital Organization, Sagamihara National Hospital, Clinical Research Center for Allergy and Rheumatology, Sagamihara, Japan.
Umezu-Goto
Makiko
M
Kobayashi
Noriaki
N
Takahashi
Kazuhisa
K
Fukuchi
Yoshinosuke
Y
Mori
Akio
A
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology; D020013:Calcium Signaling; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D040001:Dermatophagoides farinae / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D016853:Muromonab-CD3 / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014020:Tissue Extracts / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000485:Allergens; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D018106:CD28 Antigens; D017252:CD3 Complex; C508599:IL5 protein, human; C508607:IL9 protein, human; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D016906:Interleukin-9; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014020:Tissue Extracts; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate