Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints

Introduction Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate art...
Ausführliche Beschreibung

Introduction Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA. Methods To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naïve syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays. Results Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice. Conclusions Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints. Ausführliche Beschreibung

Autor*in:	Angyal, Adrienn [verfasserIn] Egelston, Colt Kobezda, Tamás Olasz, Katalin László, Anna Glant, Tibor T Mikecz, Katalin

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2010

Schlagwörter:	Synovial Fluid SCID Mouse Lymphoid Organ Synovial Fluid Sample Arthritic Ankle

Anmerkung:	© Angyal et al.; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Arthritis Research & Therapy - London : BioMed Central, 1999, 12(2010), 2 vom: 18. März
Übergeordnetes Werk:	volume:12 ; year:2010 ; number:2 ; day:18 ; month:03

Links:	Volltext

DOI / URN:	10.1186/ar2954

Katalog-ID:	SPR030833663