Objective. To investigate a potential interaction between neutrophils and T cells in rheumatoid arthritis (RA), by defining the optimal conditions for induction of class II major histocompatibility complex (MHC) expression on peripheral blood neutrophils in vitro and investigating the capacity for neutrophils to express class II MHC molecules in RA. Methods. Surface expression of class II MHC and costimulatory molecules by peripheral blood and synovial fluid (SF) neutrophils obtained from healthy controls and patients with RA was measured by How cytometry and fluorescence microscopy. Intracellular class II MHC protein and, messenger RNA (mRNA) were detected by Western blotting and Northern blotting, respectively. Results. Freshly isolated peripheral blood neutrophils from controls did not express surface class II MHC; expression was induced by culture with appropriate cytokines. Freshly isolated peripheral blood neutrophils from patients with RA expressed mRNA, but there was no surface expression of class II MHC. Freshly isolated SF neutrophils from patients with RA contained high levels of class II MHC mRNA, did not express surface class II MHC, but did have large intracellular amounts of this protein as detected by Western blotting. After culture for 20 hours in vitro, SF neutrophils from RA patients expressed large amounts of surface class II MHC hut very low levels of costimulatory molecules CD80 and CD86. Fluorescence microscopy localized surface class II MHC to discrete areas on the neutrophil. Class II MHC-expressing neutrophils stimulated T cell proliferation. Conclusion. Peripheral blood neutrophils from patients with RA but not healthy controls express class II MHC mRNA. SF neutrophils in RA synthesize and express large amounts of class II MHC but not costimulatory molecules. This might underlie a novel interaction with T cells that is important in terms of disease pathology.
机构:
Karolinska Inst, Stockholm, SwedenHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Jiang, Xia
Cui, Jing
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USA
Broad Inst, Cambridge, MA USAHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Cui, Jing
Lu, Bing
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USAHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Lu, Bing
Costenbader, Karen H.
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USAHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Costenbader, Karen H.
Sparks, Jeffrey A.
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USAHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Sparks, Jeffrey A.
Bang, So-Young
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Hanyang Univ Hosp Rheumat Dis, Seoul 133792, South KoreaHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Bang, So-Young
Lee, Hye-Soon
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Hanyang Univ Hosp Rheumat Dis, Seoul 133792, South KoreaHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Lee, Hye-Soon
Okada, Yukinori
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USA
Broad Inst, Cambridge, MA USA
Tokyo Med & Dent Univ, Tokyo, Japan
RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, JapanHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Okada, Yukinori
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Raychaudhuri, Soumya
Alfredsson, Lars
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Karolinska Inst, Stockholm, SwedenHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Alfredsson, Lars
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Bae, Sang-Cheol
Klareskog, Lars
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Karolinska Inst, Stockholm, Sweden
Karolinska Hosp, S-10401 Stockholm, SwedenHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
Klareskog, Lars
Karlson, Elizabeth W.
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Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Boston, MA USAHanyang Univ Hosp Rheumat Dis, Seoul 133792, South Korea
机构:
Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Anim Sci, Wooster, OH 44691 USAOhio State Univ, Ohio Agr Res & Dev Ctr, Dept Anim Sci, Wooster, OH 44691 USA
Cannon, MJ
Pate, JL
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Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Anim Sci, Wooster, OH 44691 USAOhio State Univ, Ohio Agr Res & Dev Ctr, Dept Anim Sci, Wooster, OH 44691 USA