Susceptibility to collagen-induced arthritis is modulated by TGFbeta responsiveness of T cells
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Susceptibility to collagen-induced arthritis is modulated by TGFbeta responsiveness of T cells. / Schramm, Christoph; Kriegsmann, Jörg; Protschka, Martina; Huber, Samuel; Hansen, Torsten; Schmitt, Edgar; Galle, Peter Robert; Blessing, Manfred.
in: ARTHRITIS RES THER, Jahrgang 6, Nr. 2, 2004, S. R114-R119.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Susceptibility to collagen-induced arthritis is modulated by TGFbeta responsiveness of T cells
AU - Schramm, Christoph
AU - Kriegsmann, Jörg
AU - Protschka, Martina
AU - Huber, Samuel
AU - Hansen, Torsten
AU - Schmitt, Edgar
AU - Galle, Peter Robert
AU - Blessing, Manfred
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - Animals
KW - Arthritis, Experimental/chemically induced
KW - Arthritis, Rheumatoid/chemically induced
KW - Cattle
KW - Cell Proliferation
KW - Cells, Cultured
KW - Collagen Type II/immunology
KW - Crosses, Genetic
KW - Cytokines/biosynthesis
KW - Disease Susceptibility
KW - Lymph Nodes/pathology
KW - Mice
KW - Mice, Inbred DBA
KW - Mice, Inbred Strains
KW - Mice, Transgenic
KW - Severity of Illness Index
KW - T-Lymphocytes/physiology
KW - Th1 Cells/metabolism
KW - Transforming Growth Factor beta/physiology
U2 - 10.1186/ar1039
DO - 10.1186/ar1039
M3 - SCORING: Journal article
C2 - 15059274
VL - 6
SP - R114-R119
JO - ARTHRITIS RES THER
JF - ARTHRITIS RES THER
SN - 1478-6354
IS - 2
ER -