Immunological and Functional Characteristics of Peripheral Blood and Synovial Fluid Lymphocytes from Patients with Rheumatoid Arthritis

Abstract

Spontaneous (SCMC) and antibody dependent cellular cytotoxicity (ADCC); mitogenic responsiveness (PHA, Con A, PPD, dextran and pokeweed) as well as lymphocyte subpopulations (E‐, EA‐, EAC‐rosettes, S‐Ig) were studied simultaneously in peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of fifteen patients with rheumatoid arthritis. Marked differences were observed in the cytotoxic activity of SFL and PBL. Whereas SCMC activity of SFL was always significantly elevated above the cytotoxic levels of PBL, the reverse was true for the ADCC reaction; here, 50% of the patients showed a decreased cytotoxicity of SFL compared to PBL. Synovial fluid neutrophils (SFN) were found to be inactive in both cytotoxic assays. No differences were found in ADCC activity of PBL between normal controls and RA patients. In SCMC assays a significantly increased activity of control PBL was only observed at L/T ratios of 100:1. Overnight incubation of PBL from RA patients and normal controls resulted in a marked decrease in SCMC and, to a smaller extent, in ADCC activity. SFL from three out of four patients lost less SCMC activity after overnight incubation than the corresponding PBL. In one patient even an increased activity in both cytotoxic systems was obtained. Regarding lymphocyte populations, T‐cells were significantly decreased in PBL of RA patients. With the exception of a significantly lowered percentage of C3 receptor positive cells in SFL, no significant differences were recorded in the lymphocyte distribution between the patients' PBL and SFL. In the RA patients, the response to T‐cell mitogens was significantly depressed in SFL while PPD and pokeweed reactivity was equal to that of PBL.

Defective monocyte cytotoxicity in rheumatoid arthritis

“…Burmester (18) reported slightly reduced spontaneous cytotoxicity of blood lymphocytes against a melanoma cell line (IGR3) in subjects with RA, but only at effector-to-target ratio of 100: 1, a ratio considerably above the 20: used in the present studies. Our finding that lymphocyte ADCC is normal in RA is in agreement with several other reports (18)(19)(20). Only Isturiz and coworkers (21) have reported decreased lymphocyte ADCC in RA.…”

Differential expression of Ia antigens by rheumatoid synovial lining cells.

“…The presence of Interferon-y has been documented both in the rheumatoid synovium (32) and the synovial fluid (33). A possible source of this mediator may be the large number of activated Ia' T cells present in this compartment (13,27,34), especially in view of the finding that Ia' T cells are the primary producers of Interferon-'y in in vitro assays (35). (39), on keratinocytes in lichen ruber planus (40), and on other cell types in various autoimmune diseases (41,42).…”

“…Characteristics of the monoclonal anti-Ia reagents are outlined in Table I (26]), whereas B cells were detected by surface immunoglobulin staining (27). All the reagents described above were used in concentrations that had been shown in extensive preliminary studies to be saturating using the fluorescence-activated cell sorter.…”

Treatment of rheumatoid arthritis with an anti‐CD4 monoclonal antibody

“…detectable infectious agents, large numbers of T lymphocytes, including the CD4+ T helperiinducer cell subset, infiltrate the synovium (1,2). Several studies have demonstrated an activated phenotype and altered functional properties of these cells (3,4). Moreover, in animal models, arthritis is inducible in healthy animals solely by the injection of arthritogenic T cell clones or lines (5).…”