New drug targets in rheumatoid arthritis: focus on chemokines.

Rheumatoid arthritis is a chronic inflammatory disease where the synovial tissue is characterized by heavy infiltration of leukocytes. Chemokines and chemokine receptors play an important role in cell migration and positioning of leukocytes within the inflamed rheumatoid synovium. There is now much focus on the specific contribution and role of each chemokine and chemokine receptor in the chronic inflammatory process in the synovial tissue.

The chemokines CCL5, CCL2 and CXCL12 play significant roles in the migration of Th1 cells into rheumatoid synovial tissue.

As the T-cell population in the synovial tissue (ST) in rheumatoid arthritis (RA) is dominated by T helper (Th) 1 cells, this study was designed to examine whether there is a preferential migration of polarized T cells to ST, and to identify the chemokines responsible for the migration. This was done by developing 10 T-cell clones specific for an arbitrary antigen (mouse immunoglobulin G (IgG)) from the peripheral blood (PB) of a healthy donor sensitized to mouse IgG. The Th polarizations of the clones were determined by measuring secreted interferon-gamma and interleukin-4, following anti-CD3 stimulation.

Association of antigen specificity and migratory capacity of memory T cells in rheumatoid arthritis.

Among the T cell pool of multiple specificities in the rheumatoid synovial tissues (ST) we have previously shown a lack of proliferative response of T cells to Acanthamoeba polyphaga [1]. In contrast, peripheral blood (PB) derived T cells proliferate to the antigen. The aim of the present study was to establish whether there is a preferential migration of some T cell specificities to the joint in rheumatoid arthritis (RA) patients dependent on the chemokine system, and to identify which chemokine receptors are involved in the migratory process.

T-cell responses to viral, bacterial and protozoan antigens in rheumatoid inflammation. Selective migration of T cells to synovial tissue.

Objective: To identify any preferential or selective migration of T-cell specificities to inflamed tissues of rheumatoid arthritis (RA) patients.

Methods: Lymphocytes from peripheral blood (PB) and synovial tissue (ST) were isolated from RA patients and stimulated with a panel of crude antigen preparations from 18 bacterial, protozoan and viral sources. Proliferative responses of the T lymphocytes to each antigen and group of antigens were compared in PB and ST.