Susceptibility to collagen-induced arthritis is modulated by TGFbeta responsiveness of T cells.
The objective of our study was to determine the regulatory effects that endogenous transforming growth factor beta (TGFbeta) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFbeta type II receptor in T cells under the control of the human CD2 promoter. Clinical and histological arthritis scores were determined and experiments on disease induction and the healing phase of disease were performed. The proliferation and cytokine production of draining lymph node cells in vitro were analyzed. Transgenic mice were more susceptible to induction of CIA. The overall incidence was higher in transgenic mice than in wild-type mice (57% vs 35%, P < 0.05). Affected transgenic animals displayed a significantly higher clinical (4.5 +/- 0.6 vs 1.67 +/- 0.19, P = 0.001) and histological arthritis score (8.01 +/- 0.9 vs 4.06 +/- 1.1, P < 0.05). Draining lymph node cells of transgenic mice secreted more tumor necrosis factor alpha and IFNgamma and proliferated more vigorously in response to collagen type II and upon CD3/CD28 costimulation in vitro. Therefore, the regulation of T cells by endogenous TGFbeta is important for the maintenance of joint integrity after arthritis induction. Defects in TGFbeta-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation.
Schramm
Christoph
C
I, Medizinische Klinik, Johannes Gutenberg-Universität Mainz, Mainz, Germany. schramm@uni-mainz.de
Kriegsmann
Jörg
J
Protschka
Martina
M
Huber
Samuel
S
Hansen
Torsten
T
Schmitt
Edgar
E
Galle
Peter Robert
PR
Blessing
Manfred
M
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology*; D018417:Th1 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D024043:Collagen Type II; D016207:Cytokines; D016212:Transforming Growth Factor beta