Rheumatoide Arthritis - eine T-Zell-abhängige Erkrankung

Zusammenfassung

T-Zellen, insbesondere CD4+-T-Zellen, sind für viele Aspekte der rheumatoiden Entzündungsreaktion verantwortlich. So zeigen CD4+-T-Zellen von Patienten mit rheumatoider Arthritis sowohl in der entzündeten Synovialmembran als auch in der peripheren Zirkulation eine Reihe von funktionellen Veränderungen, die sie als proinflammatorische Effektorzellen ausweisen. Andererseits legen neuere Erkenntnisse nahe, dass die Rolle von CD4+-T-Zellen in der Pathogenese der rheumatoiden Entzündung weit über die der aktivierten Effektorzellen, die eine chronische Autoimmunreaktion initiieren und unterhalten, hinausgeht. Neuere Daten lassen vermuten, dass die Funktion von CD4+-T-Zellen mit immunmodulierender Fähigkeit, wie z. B. T-Helfer-Typ - 2-Zellen oder die Gruppe der CD25+ regulatorischen T-Zellen bei Patienten mit rheumatoider Arthritis geschwächt ist. Dieser Funktionsverlust von Untergruppen von CD4+-T-Zellen mit regulatorischer Funktion stellt einen wichtigen pathogenetischen Mechanismus der Erkrankung dar, da er vermutlich den Zusammenbruch der peripheren Toleranz zu Beginn der Autoimmunreaktion und damit die Entwicklung und Chronifizierung der autoantigenspezifischen T-Zell-Aktivierung ermöglicht.

Abstract

T cells, in particular CD4+ T cells, are responsible for many aspects of rheumatic inflammation. It has been demonstrated that CD4+ T cells from patients with rheumatoid arthritis express a variety of abnormalities, both in the inflamed synovium as well as in the peripheral circulation, that identify them as proinflammatory effector cells. Recent evidence, however, suggests that the role of CD4+ T cells in the pathogenesis of rheumatic inflammation is not restricted to that of activated effector cells initiating and perpetuating chronic autoimmune inflammation. Recent data suggest that the function of CD4+ T cells with an immunomodulatory capability, such as T helper type 2 cells or the population of CD25+ regulatory T cells, is impaired in patients with rheumatoid arthritis. This functional abnormality of subgroups of CD4+ T cells with a regulatory capacity presents an important mechanism in the pathogenesis of the disease as it might allow the breakdown of peripheral tolerance at the initiation of the autoimmune reaction, promoting the development and perpetuation of autoantigen-specific T cell activation.

Schlüsselwörter

T-Zelle - rheumatoide Arthritis - Autoimmunität - Immunregulation - Genetik

Key words

T cells - rheumatoid arthritis - autoimmunity - immune regulation - genetics

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