Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing antigen presentation with concomitant decrease of HLA-DQ antigen on macrophages.
Allergen activates T lymphocytes responsive to interleukin 2 (IL-2) in allergic patients but not in normal individuals. This response was suppressed by anti-allergic agent, Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo [4, 5] cyclohepta [1, 2-b] thiophen-10 (9H)-one hydrogen (fumarate). Prolonged culture of antigen-presenting adherent cells impaired the ability to present Dermatophagoides farinae (Df) antigen to T cells, whereas stimulation of adherent cells with recombinant interferon-gamma (IFN-gamma) restored the antigen-presenting capability. The maintained antigen presenting ability of adherent cells treated with IFN-gamma was also suppressed by Ketotifen. Fluorescence activated cell sorter (FACS) analysis disclosed that Ketotifen selectively reduced the expression of HLA-DQ antigen, crucial restriction elements in Df antigen-related responses, on macrophages but not on B cells, even in the presence of IFN-gamma. Collectively, Ketotifen prevented macrophages from inducing allergen-activated T lymphocytes' responsiveness to IL-2 at least in part by decreasing the expression of HLA-DQ antigen.
Kawano
Y
Y
Department of Pediatrics, Saitama Medical School, Japan.
Yoshizawa
I
I
Baba
M
M
Noma
T
T
D000293:Adolescent; D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects*; D001249:Asthma / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006683:HLA-DQ Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007665:Ketotifen / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D018926:Anti-Allergic Agents; D006683:HLA-DQ Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D007665:Ketotifen