Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis.
J Immunol
; 159(6): 2973-8, 1997 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-9300721
ABSTRACT
In rheumatoid arthritis (RA), the functional status of T cells is incompletely understood. Synovial T cells display phenotypic evidence of former activation, but there is poor production of T cell-derived cytokines in the synovium. In addition, synovial T cell proliferation upon mitogenic and antigenic stimulation was decreased compared with that in peripheral blood T cells. Moreover, previous reports revealed that early Ca2+ rises induced by TCR/CD3 stimulation were decreased in RA T cells compared with those in healthy controls. To investigate the molecular mechanisms of RA synovial T cell hyporesponsiveness, we analyzed the TCR/CD3-mediated protein tyrosine phosphorylation in RA peripheral blood and synovial fluid (SF) T cells. SF T cells exhibited a decreased overall tyrosine phosphorylation pattern upon stimulation. Most notably, the induction of phosphorylation of p38 was virtually absent. Moreover, we found that tyrosine phosphorylation of the TCR zeta-chain, one of the most proximal events in TCR signaling, is clearly diminished in RA SF T cells. The decrease in tyrosine phosphorylation was accompanied by a decrease in detectable levels of zeta-protein within synovial T cells. These results suggest that a defective TCR signaling underlies the hyporesponsiveness of synovial T cells in RA.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Membrana Sinovial
/
Receptores de Antígenos de Linfocitos T
/
Linfocitos T
/
Transducción de Señal
/
Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
1997
Tipo del documento:
Article
País de afiliación:
Países Bajos