Increased expression of the CD80 accessory molecule by alveolar macrophages in asthmatic subjects and its functional involvement in allergen presentation to autologous TH2 lymphocytes |
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Authors: | Samuele E. Burastero MDa Zulma Magnani PhDa Claudio Confetti PhDa Laura Abbruzzese MDa Susanna Oddera PhDb Piero Balbo MDd Giovanni A. Rossi MDb Emanuele Crimi MDc |
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Affiliation: | a Milan, Genoa, and Vercelli, Italy;b From athe Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan; bG. Gaslini Institute; cthe Chair of Respiratory Physiology, University of Genoa, Genoa; and dAOR 11, Ospedale di Gattinara, Vercelli |
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Abstract: | Background: Alveolar macrophages (AMs) are more efficient antigen-presenting cells in allergic individuals than in nonatopic subjects. Objective: We studied whether this difference may be correlated to increased expression of membrane costimulatory molecules, such as the B7 molecules (CD80 and CD86). Methods: Eleven subjects with allergic asthma sensitized to Dermatophagoides pteronyssinus and 5 healthy nonatopic volunteers underwent bronchoalveolar lavage, and the costimulatory molecule expression on AMs was evaluated. Peripheral blood T cells, either freshly isolated or as established D pteronyssinus -specific cell lines, were cultured with autologous monocytes or AMs as antigen-presenting cells. In vitro allergen-induced proliferation and cytokine production were evaluated in the presence of B7-blocking reagents. Results: Allergic individuals had a significantly higher proportion of AMs expressing the CD80 molecule than control subjects (28.5% ± 14.8% vs 1.4% ± 1.2%; P < .001), whereas no difference was observed in CD86 expression (2.0% ± 2.3% vs 1.1% ± 0.6; P > .1). In a large proportion of the asthmatic subjects we studied, AMs were presenting soluble antigens (tetanus toxoid and streptolysin-O) to freshly isolated T cells more efficiently than AMs from nonatopic control subjects. Finally, both T-cell proliferation and cytokine production of D pteronyssinus- specific established T-cell lines were inhibited by a CD80-blocking antibody in a dose-dependent manner. Conclusion: Costimulation by means of CD80 expressed by AMs is probably involved in the amplification of the allergen-specific T-lymphocyte response in the airways of asthmatic subjects. (J Allergy Clin Immunol 1999;103:1136-42.) |
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Keywords: | Allergy asthma monocyte-macrophages antigen presentation costimulation CD80 CD86 |
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