The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium

Abstract

Objective. To investigate the expressions of costhulatory molecules CD86 (B7-2, B70) and CD28 by cells obtained from the synovial tissues (ST) and synovial fluids (SF) of patients with rheumatoid arthritis (RA).Methods. Monoclonal antibodies (MAb) against CD86 and CD28 were used for immunochemical study of synovia from 18 RA patients, 4 osteoarthritis (OA) patients, and 4 normal subjects. These MAb were also used for flow cytometry of isolated ST cells from 8 RA and 5 OA patients and of SF mononuclear cells from 5 RA and 5 OA patients.Results. Immunohistochemical examination revealed that CD86+ cells occurred in 11 of the 18 RA synovia, but in none of the 4 OA or 4 normal synovia. Most of the positive cells had macrophage-like morphology, and surrounded lymphoid aggregates. Most cells within lymphoid aggregates were stained positively for CD28. Flow cytometry showed that CD86+ cells comprised 2.9-33.4% (average 14.3%) of the total ST cells and 2.1-14.9% (average 6.1%) of the total SF mononuclear cells from RA patients. Approximately 40% of the CD86+ cells expressed CD14. A majority (mean 72%, range 57439%) of the T cells in ST and SF expressed CD28. RA synovia expressed more CD86 molecules than did OA synovia (mean frequency of positive cells 14.3% versus 2.8%; mean fluorescence intensity 104.6 versus 40.9).Conclusion. This study has shown that the exMing Fei Liu, MD: National Cheng Kung University, Tainan, Taiwan, Republic of China; Hitoshi Kohsaka, MD, Hiroshi Sakurai, BSc, Ichiro Saito, DDS, PhD, Nobuyuki Miyasaka, MD: Tokyo Medical and Dental University, Tokyo, Japan; Miyuki Azuma, PhD, KO Okumura, MD: School of Medicine, Juntendo University, Tokyo, Japan.Address reprint requests to Ming Fei Liu, MD, Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.Submitted for publication February 17, 1995; accepted in revised form June 23, 1995. pression of the CD86 molecule was up-regulated in RA synovia. The CD86+ c e k appeared macrophage-like and surrounded CD28+ cells in lymphoid aggregates. The simultaneous presence and close localization of CD86+ and CD28+ cells in the RA synovial compartment suggests that their interaction potentially contributes to the sustained immune activation of RA.Optimal T cell activation requires a costimulatory signal in addition to the primary signal provided by T cell receptor cross-linkage (1). The earliest example of the costimulatory signals discovered was the interaction between the CD28 on T lymphocytes and the B7 on antigen-presenting cells (2-5). Recently, another molecule, CTLA-4, was found to have homologous structure with CD28 and to bind to B7 (6,7). There is evidence that ligands of CD28 and CTLA-4 consist of CD80 (B7-1) and CD86 (B70, B7-2) (8-13). It has been shown that CD86 is constitutively expressed on fresh monocytes, whereas CD80 requires further lipopolysaccharide (LPS) stimulation. Compared with CDHO, CD86 on monocytes and B cells are upregulated at much higher levels and more rapidly by activation with interferon...

Differential regulation of rheumatoid synovial cell interleukin-12 production by tumor necrosis factor ? and CD40 signals

“…Indeed, macrophage-lineage cells in rheumatoid synovium express Table 2. Effect of rolipram on IL-12 p40 and TNF␣ production by synovial cells from RA patients in the absence or presence of LPS* higher amounts of costimulatory molecule CD86 and chronic inflammation marker 25F9 compared with those in OA SC (31,32). These phenotypic differences in SC may result in the inequality in IL-12 production between synovial tissue from patients with RA and that from patients with OA.…”

CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in southeastern China

“…CD86 activates T-cells and regulates the immune response, CD86 deficiency led to impairments in dendritic cells, B-lymphocytes, and macrophages (Yadav and Sarvetnick, 2007). The expression of the CD86 molecule was upregulated in RA synovia (Liu et al, 1996). Peripheral B-cells from RA patients have an altered expression of CD86 (Catalan et al, 2010).…”

Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig

“…These antigen-presenting cells are activated and express both class II MHC and costimulatory molecules such as CD80 (B7-1) and CD86 (B7-2). [13][14][15][16][17] These observations suggest that synovial T cells, macrophages, dendritic cells, and B cells may have a direct role in the disease process.…”