Abstract
We demonstrated previously that CD81(-/-) mice have an impaired Th2 response. To determine whether this impairment affected allergen-induced airway hyperreactivity (AHR), CD81(-/-) BALB/c mice and CD81(+/+) littermates were sensitized i.p. and challenged intranasally with OVA. Although wild type developed severe AHR, CD81(-/-) mice showed normal airway reactivity and reduced airway inflammation. Nevertheless, OVA-specific T cell proliferation was similar in both groups of mice. Analysis of cytokines secreted by the responding CD81(-/-) T cells, particularly those derived from peribronchial draining lymph nodes, revealed a dramatic reduction in IL-4, IL-5, and IL-13 synthesis. The decrease in cytokine production was not due to an intrinsic T cell deficiency because naive CD81(-/-) T cells responded to polyclonal Th1 and Th2 stimulation with normal proliferation and cytokine production. Moreover, there was an increase in T cells and a decrease in B cells in peribronchial lymph nodes and in spleens of immunized CD81(-/-) mice compared with wild-type animals. Interestingly, OVA-specific Ig levels, including IgE, were similar in CD81(-/-) and CD81(+/+) mice. Thus, CD81 plays a role in the development of AHR not by influencing Ag-specific IgE production but by regulating local cytokine production.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Intranasal
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Allergens / administration & dosage*
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Allergens / immunology
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Animals
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Antigens, CD / genetics*
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B-Lymphocytes / pathology
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Bronchial Hyperreactivity / genetics*
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Bronchial Hyperreactivity / immunology*
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Bronchial Hyperreactivity / pathology
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Bronchial Hyperreactivity / prevention & control
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Cytokines / antagonists & inhibitors
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Cytokines / biosynthesis
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Down-Regulation / genetics
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Down-Regulation / immunology
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Eosinophilia / genetics
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Eosinophilia / metabolism
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Eosinophilia / pathology
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Eosinophilia / prevention & control
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Epitopes, T-Lymphocyte / immunology
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Immunoglobulin E / biosynthesis
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Immunologic Deficiency Syndromes / genetics
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Immunologic Deficiency Syndromes / immunology
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Inflammation / genetics
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Inflammation / metabolism
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Inflammation / prevention & control
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Injections, Intraperitoneal
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Interphase / genetics
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Interphase / immunology
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Lung / metabolism
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Lung / pathology
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Lymph Nodes / pathology
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Lymphocyte Activation / genetics
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Lymphocyte Count
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Lymphopenia / genetics
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Lymphopenia / immunology
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Lymphopenia / pathology
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Membrane Proteins*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mucins / biosynthesis
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Species Specificity
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Spleen / pathology
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Tetraspanin 28
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Allergens
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Antigens, CD
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Cd81 protein, mouse
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Cytokines
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Epitopes, T-Lymphocyte
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Membrane Proteins
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Mucins
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Tetraspanin 28
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Immunoglobulin E
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Ovalbumin