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Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing antigen presentation with concomitant
Y Kawano1, I Yoshizawa, M Baba
1Department of Pediatrics, Saitama Medical School, Japan.
Asian Pacific Journal of Allergy and Immunology
|December 1, 1996
Summary
Ketotifen, an anti-allergic drug, suppresses T lymphocyte responses to allergens by reducing HLA-DQ antigen expression on macrophages. This mechanism inhibits allergen-induced interleukin-2 (IL-2) responsiveness in allergic patients.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Allergic patients exhibit T lymphocyte activation by allergens, leading to interleukin-2 (IL-2) responsiveness, unlike normal individuals.
- Antigen-presenting cells (APCs) are crucial for T cell activation, and their function can be modulated by cytokines and pharmacological agents.
- Dermatophagoides farinae (Df) is a common allergen implicated in allergic diseases.
Purpose of the Study:
- To investigate the mechanism by which the anti-allergic agent Ketotifen suppresses allergen-induced T lymphocyte activation.
- To determine the effect of Ketotifen on the antigen-presenting capacity of macrophages and their interaction with T cells.
- To elucidate the role of HLA-DQ antigen expression in Ketotifen's anti-allergic effects.
Main Methods:
- Cell culture of antigen-presenting adherent cells.
- Stimulation of adherent cells with recombinant interferon-gamma (IFN-gamma).
- Treatment with the anti-allergic agent Ketotifen.
- Fluorescence activated cell sorter (FACS) analysis to assess antigen expression on immune cells.
- Assessment of T lymphocyte responsiveness to interleukin-2 (IL-2).
Main Results:
- Ketotifen suppressed the allergen-induced T lymphocyte response to IL-2 in allergic patients.
- Interferon-gamma (IFN-gamma) restored the antigen-presenting ability of aged adherent cells.
- Ketotifen treatment reduced the expression of HLA-DQ antigen on macrophages, a key molecule for antigen presentation.
- This reduction in HLA-DQ expression by Ketotifen occurred even in the presence of IFN-gamma and was specific to macrophages, not B cells.
Conclusions:
- Ketotifen exerts its anti-allergic effect, at least in part, by inhibiting macrophages' ability to induce T lymphocyte responsiveness to IL-2.
- The mechanism involves the downregulation of HLA-DQ antigen expression on macrophages.
- These findings provide insights into the immunomodulatory actions of Ketotifen in allergic responses.