Central Role of Thrombospondin-1 in the Activation and Clonal Expansion of Inflammatory T Cells

Thrombospondin-1 (TSP) is a transiently expressed matricellular protein known to promote chemotaxis of leukocytes to inflammatory sites. However, TSP and its receptor CD36 are abundantly expressed in chronically inflamed tissues such as the rheumatoid synovium. Here, we show that TSP provides the co...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2000-03, Vol.164 (6), p.2947-2954
Main Authors: Vallejo, Abbe N, Mugge, Lars O, Klimiuk, Piotr A, Weyand, Cornelia M, Goronzy, Jorg J
Format: Article
Language:English
Subjects:
Antigens, CD - immunology
Antigens, CD - metabolism
Antigens, CD - physiology
Arthritis, Rheumatoid - immunology
Biopolymers - metabolism
Carrier Proteins - immunology
Carrier Proteins - metabolism
Carrier Proteins - physiology
CD36 antigen
CD36 Antigens - metabolism
CD47 Antigen
Cell Line
Clone Cells
Coculture Techniques
Fibroblasts - immunology
Fibroblasts - pathology
HLA-DR Antigens - immunology
Humans
Inflammation - immunology
Lymphocyte Activation - immunology
Synovial Membrane - immunology
Synovial Membrane - pathology
synoviocytes
T-Lymphocytes - immunology
T-Lymphocytes - pathology
thrombospondin 1
Thrombospondin 1 - metabolism
Thrombospondin 1 - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Thrombospondin-1 (TSP) is a transiently expressed matricellular protein known to promote chemotaxis of leukocytes to inflammatory sites. However, TSP and its receptor CD36 are abundantly expressed in chronically inflamed tissues such as the rheumatoid synovium. Here, we show that TSP provides the costimulatory signal that is necessary for the activation of autoreactive T cells. Data presented reveal that TSP-mediated costimulation is achieved through its independent interaction with CD36 on APCs and with CD47 on T cells. We propose that a CD47-TSP-CD36 trimolecular complex is a novel costimulatory pathway that significantly decreases the threshold of T cell activation. Consistent with the paradigm that lesions in rheumatoid synovitis are sites of antigenic recognition, the characteristic focal expression of TSP on APCs such as macrophages and fibroblast-like synoviocytes suggest a central role of TSP in the expansion of tissue-infiltrating T cells.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.164.6.2947