T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy.

Abstract:

:Although thyroid-associated ophthalmopathy (TAO) is now generally accepted as an autoimmune inflammatory disorder of the extraocular muscles and the orbital connective tissue, its aetiopathogenesis remains poorly understood. Recent data indicate that impaired interactions between T cells and extracellular matrix (ECM) proteins may play an important role in development and maintaining of an inflammatory process. We report here results of the study focusing on interactions between T lymphocytes and collagen-I (Coll-I), collagen-IV (Coll-IV), fibronectin (FN), laminin (LM) in patients with TAO. Using a standard peripheral blood mononuclear cells (PBMC) proliferation assay, we observed a markedly enhanced T cell response to Coll-I in patients with active TAO (mean SI=4.5). The proliferatory response to Coll-I was significantly greater (Wilcoxon test; p < 0.001) than in normal subjects (mean SI=1.88), patients with stable TAO (mean SI=2.05) and patients with thyroid autoimmune diseases (AITD) without ophthalmopathy (mean SI=2.49). PBMC stimulation by Coll-I is likely to be antigen-dependent requiring engagement of the T cell receptor with collagen peptides, rather than mediated via integrins. The percentage of circulating CD29+ (beta1 integrin chain) T cells was not increased in patients with active TAO. Additionally in the assay of costimulation of CD3-mediated proliferation, we found that peripheral blood T cells from patients with TAO and AITD were costimulated only by FN. On the other hand a markedly enhanced costimulation of CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed in a retrobulbar T cell line. We conclude that abnormalities in T cell interactions with ECM proteins, especially Coll-I may play a role in the pathogenesis of TAO.

journal_name

Autoimmunity

journal_title

Autoimmunity

authors

Bednarczuk T,Kiljanski J,Mrowiec T,Slon M,Ing E,Stolarski C,Kennerdell JS,Gorski A,Nauman J,Wall JR

doi

10.3109/08916939808993834

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

221-30

issue

4

eissn

0891-6934

issn

1607-842X

journal_volume

27

pub_type

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