Induction of Th2 cell tolerance to a soluble antigen by blockade of the LFA-1-dependent pathway prevents allergic inflammation.
In this article, we show that induction of Th2 cell tolerance prevents antigen-induced eosinophil recruitment into the tissue and IgE antibody production, and that ICAM-1/LFA-1 interaction is involved as a costimulatory signal in inducing T cell tolerance to a soluble antigen. In vivo pretreatment with anti-ICAM-1 monoclonal antibody (mAb), anti-LFA-1 mAb, and a soluble antigen inhibited antigen-induced eosinophil recruitment into the airways and IgE antibody production in mice in an antigen-specific manner. In vitro antigen-induced IL-2, IL-4 and IL-5 production were decreased in spleen cells of the mice pretreated with the two mAbs and the antigen, indicating the induction of both Th1 and Th2 cell tolerance in vivo. These results suggest that the induction of antigen-specific Th2 cell tolerance by allergen immunotherapy with blockade of the ICAM-/LFA-1 interaction would be a rational therapeutic approach to allergic inflammation such as asthma.
Iwamoto
I
I
Department of Internal Medicine, Chiba University School of Medicine, Japan.
Nakao
A
A
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*
D018106:CD28 Antigens; D007376:Interleukin-2; D015848:Interleukin-5; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007073:Immunoglobulin E