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.
Department of Internal Medicine II, Chiba University School of Medicine, Chiba City, Japan.
M
M
Kasai
K
K
Kumano
K
K
Kurasawa
A
A
Nakao
Y
Y
Saito
I
I
Iwamoto
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