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URN: urn:nbn:de:bsz:25-opus-8160
URL: http://www.freidok.uni-freiburg.de/volltexte/816/


Barth, Jan Thomas

Hyporesponsive synovial fluid T cells in rheumatoid Arthritis

Anerge Synovialflüssigkeits-T-Zellen in Rheumatoider Arthritis

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Kurzfassung in Deutsch

Rheumatoid arthritis is a chronic, usually progressive inflammatory disorder of joints in which the immune system plays a central role in pathogenesis. Both chronically inflamed synovial tissue and synovial fluid (SF) are usually rich in infiltrated CD4+ T helper cells (TH cells) and CD8+ cytotoxic T cells (CTL). Only T cells isolated from the SF of many RA patients were anergic upon their activation in vitro by stimulation of the T cell receptor and the co-stimulatory receptor CD28 which means that these T cells did not proliferate. In vitro-activated anergic SF T cells from RA patients were able to express most activation-dependent genes (e.g. CD69, CD25, CD152, IL-13 and IFN-g), although T cells did not proliferate. The main cause for the impaired proliferation of RA SF T cells is the absent expression of T cell growth factor IL-2. The detailed analysis of the hyporesponsive state of RA SF T cells and comparison with other models of T cell anergy (clonal anergy and peripheral tolerance), T cell suppressions (TR1 cells and CD25+ TS cells) and replicative senescent T cells suggested that this kind of T cell hyporesponsiveness is different. T cell hyporesponsiveness is obviously induced by a soluble factor, which is present in the synovial fluid of RA patients that contained anergic SF T cells. The identity, origin and function of the proposed factor still has to be determined. Furthermore, T cells from the synovial fluid of RA patients are also hyporesponsive to induction of CD95L/CD95-mediated apoptosis, although they express the death receptor CD95. The determination of different SF T cell phenotypes based on their differential expression of chemokine receptors CCR7 and CXCR6 (Bonzo), the recently described marker for replicative senescence KLRG1 and the effector/memory marker CD45RO revealed that the populations of T cells present in the SF from arthritis patients with anergic and normally proliferating T lymphocytes are similar in seize and composition.


SWD-Schlagwörter: Rheumatoide Arthritis , T-Lymphozyt , Proliferation , Inhibition , Chemokine , Zytokine
Freie Schlagwörter (deutsch): Anergie
Institut: Institut für Biologie 2
Fakultät: Fakultät für Biologie (bis Sept. 2002)
DDC-Sachgruppe: Biowissenschaften, Biologie
Dokumentart: Dissertation
Erstgutachter: Eibel, Hermann (Dr.)
Sprache: Englisch
Tag der mündlichen Prüfung: 18.07.2003
Erstellungsjahr: 2003
Publikationsdatum: 18.09.2003
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