Blockade of CD28/B7 interaction suppresses allergic eosinophilic inflammation in mice.
To determine whether the costimulatory signal via CD28/B7 interaction is required for causing allergic inflammation, we examined the effect of administration of CTLA4-Ig, a fusion protein of the extracellular domain of CTLA4 and human IgG1-constant region, at the time of sensitization, on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on IL-2, IFN-gamma, IL-4 and IL-5 production in the airways of the mice and on antigen-specific IgE synthesis in the mice. Administration of CTLA4-Ig at the time of sensitization suppressed antigen-induced eosinophil infiltration into the trachea and antigen-specific IgE production in mice. Furthermore, CTLA4-Ig administration at the time of sensitization suppressed not only IL-2 production but also IFN&hyphengamma and Th2 cytokine IL-4 and IL-5 production in the airways. Because allergic inflammation requires CD4+ T cells producing Th2-type cytokines IL-4 and IL-5, our results suggest that the costimulatory signal via CD28/B7 interaction is important for the generation and activation of Th2 cells and thereby for the development of allergic inflammation.
Kasai
M
M
Department of Internal Medicine II, Chiba University School of Medicine, Chiba City, Japan.
Kumano
K
K
Kurasawa
K
K
Nakao
A
A
Saito
Y
Y
Iwamoto
I
I
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007114:Immunization; D018796:Immunoconjugates; D007073:Immunoglobulin E / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology; D014132:Trachea / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D000069594:Abatacept; D007371:Interferon-gamma