Trans-Differentiation of polymorphonuclear neutrophils to dendritic-like cells in the synovial fluid in Rheumatoid Arthritis: evidence for activation by T-cells

Christof Iking-Konert ^1*, Benedikt Ostendorf ¹, Oliver Sander ¹, Markus Jost ², Christof Wagner ³, Leo Joosten ⁴, Matthias Schneider ¹ and Maria G. Haensch ⁵

¹ Center for Rheumatology, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf, Germany
² Department of Rheumatology, Evangelisches Fachkrankenhaus Ratingen, Germany
³ Klinik für Unfall- und Wiederherstellungschirurgie, Unfallklinik Ludwigshafen, Germany
⁴ Rheumatology Research Lab. and Advanced Therapeutics, Department of Rheumatology, Nijmegen, Netherlands
⁵ Institute for Immunology, Ruprecht-Karls University of Heidelberg, Germany

^* To whom correspondence should be addressed. E-mail: iking-konert{at}med.uni-duesseldorf.de.

Accepted 14 March 2005

Abstract

Objectives: To investigate infiltrated cells in synovial fluid (SF) in inflamed joints of patients with RA, with special reference to polymorphonuclear neutrophils (PMN) and their interaction with T-cells.

Methods: Expression on PMN of activation- associated receptors CD14, CD64, CD83, and MHC class II was examined in SF of 15 RA-patients, as were the infiltrated T-cells. SF-cytokines were determined by ELISA. To mimic the in vivo situation, co-culture experiments were carried out using PMN and T-cells of healthy donors.

Results: The SF contained activated T-lymphocytes and abundant PMN. Compared to peripheral blood, on SF- PMN expression of CD14 and CD64 was enhanced. Of special interest was that only the SF-PMN expressed MHC class II antigens and CD83. Exposure to SF, which contained considerable amounts of cytokines (e.g. IFN, TNF& [alpha], and IL2), induced a similar receptor pattern on blood derived PMN of healthy donors. Furthermore, PMN acquired MHC class II and CD83 within 24 h to 48 h, when co-cultured with autologues T-cells or T-cell-lines. This effect was also achieved by T-cell- supernatants, was dependent on protein synthesis and could be inhibited by antibodies against IFN.

Conclusions: SF-PMN from patients with RA undergo major alterations, including transdifferentiation to cells with dendritic-like characteristics, most likely induced by T-cell-derived cytokines. Since MHC class II positive PMN are known to activate T-cells, the mutual activation of PMN and T-cells could contribute to the perpetuation of the local inflammatory, and eventually to the destructive process in RA.

Keywords: CD83, MHC class II, PMN, inflammation, rheumatoid arthritis

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