T Cells and T-Cell Cytokine Transcripts in the Synovial Membrane in Patients with Osteoarthritis

Abstract

The synovial membrane in osteoarthritis (OA) often exhibits inflammatory infiltrates, but the role of T cells in these infiltrates is not known. T-cell activation antigens were analyzed by immunohistochemistry, and T-cell cytokine transcripts were measured by competitive PCR in synovial membranes from patients with OA and rheumatoid arthritis (RA). Lymphoid cell aggregates, containing primarily CD3+ T lymphocytes, were found in 65% of patients with OA. Mononuclear cells expressing the activation antigens CD69, CD25, CD38, CD43, CD45RO, and HLA class II were present in both patient groups, although in higher numbers in patients with RA. Interleukin 2 (IL-2) transcripts were found in 10 of 18 patients with OA versus 12 of 13 patients with RA (P = 0.03). Gamma interferon (IFN-γ) transcripts were detected in 9 of 18 patients with OA versus 10 of 13 patients with RA (not significant), whereas IL-10 transcripts were found in nearly all patients. IL-4 and IL-5 were not detected in any patients. The levels of IFN-γ and IL-2 transcripts, normalized for T-cell number equivalents, were not statistically different between OA and RA, but the levels of IFN-γ, normalized for total cell number equivalents, were lower in OA than in RA (P = 0.01). Synovial membranes that expressed IL-2 and IFN-γ transcripts were more likely to have heavier infiltrations of T cells and cells bearing activation markers than synovial membranes that did not express these cytokines. The presence of activated T cells and TH1 cytokine transcripts in chronic joint lesions of patients with OA suggests that T cells contribute to chronic inflammation in a large proportion of these patients.

The role of T cells in the pathogenesis of osteoarthritis

“…All of these observations in patients with OA are in addition to the findings in patients with the relatively uncommon type of erosive inflammatory disease, which clearly shows a strong inflammatory component (26). In certain patients with OA, the MNC infiltrates resemble those observed in the synovial membrane of patients with RA (18,24). Nodular lymphocytic aggregates were observed in 14% of patients with early OA (22) and in 37% (22) to 65% (24) of patients with advanced OA at the time of joint replacement surgery.…”

“…A predominant Th1 cytokine pattern has also been observed in the synovial membrane of patients with RA (24,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). Quantitative PCR analysis using MIMIC demonstrated that IFN␥ transcript levels in OA were similar to those in RA, when normalized for T cell equivalents (24). This means that T cells infiltrating the synovial membrane of patients with OA are as active as those infiltrating the synovial membrane of patients with RA, although they are present in lower numbers in OA (24).…”

“…Several groups of investigators (18)(19)(20)(21)(22)(23), including our own (24,25), have reported the presence of mononuclear cell (MNC) infiltrates consisting of T cells and macrophages in the synovial membrane of Ͼ50% of patients with OA. MNC infiltrates may be diffuse or perivascular nodular (18,24,25). We have observed angiocentric infiltrates composed primarily of CD3ϩ T cells in the synovial membrane of patients with OA ( Figure 1), in a pattern similar to that observed in RA (ref.…”

“…IL-4 or IL-5 transcripts were not detected by polymerase chain reaction (PCR) amplification in the synovial membrane of patients with OA, suggesting the presence of a Th1 cytokine pattern in the synovial membrane of patients with OA (24). A predominant Th1 cytokine pattern has also been observed in the synovial membrane of patients with RA (24,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). Quantitative PCR analysis using MIMIC demonstrated that IFN␥ transcript levels in OA were similar to those in RA, when normalized for T cell equivalents (24).…”

Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain

“…(96) T cells in the synovial membrane participate in OA inflammation and pathogenesis. (97,98) It is important to understand how VEGF signaling interactions among OA tissues may be occurring because multiple tissues are affected at the joint during OA progression. As discussed previously, VEGF expression is increased in the cartilage, (16)(17)(18)(19)(20)(21)(22)(23) synovium, (25)(26)(27)(28)(29) and subchondral bone (35)(36)(37) in OA.…”