Eosinophils facilitate antigen-specific T-cell proliferation and aggravate antigen-induced arthritis.
In the pathophysiology of rheumatoid arthritis (RA), various types of cells, including macrophages, lymphocytes, neutrophils, mast cells, osteoclasts, chondrocytes, and fibroblast-like synoviocytes, contribute to the destructive process. Involvement of eosinophils in RA was first suggested by the presence of eosinophilic cationic protein in the synovial fluid. Later, infiltration of eosinophils in the synovium of RA and the increase of eotaxin in the sera of early RA were reported. Despite these indications, the precise role of eosinophils in RA remains unclear. In this study, we analyzed whether eosinophils are involved in antigen-induced arthritis (AIA). AIA utilizes Complete Freund's adjuvant (CFA) as an inducer of the Th1 immune response and heat-killed Bordetella pertussis as a Th2 immune response inducer. We then used flow cytometry to examine whether eosinophils were present in the knee synovium of animals subjected to AIA. The results revealed that the average total cell number in synovia injected with methylated BSA (mBSA) was 4.8-fold of that in control synovium injected with saline. The numbers of eosinophils in the synovium increased 10.8-fold compared with those in the controls. We also analyzed the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, TNFα , and IL-17 ), Th1/Th2 cytokine (IFNγ and IL-13 ), and mediators that increase eosinophils (IL-5, IL-33, GM-CSF, CCL11, CCL24, CCL26, and RANTES ) in the synovium of the knee joints. The result showed that the levels of IL-17 in the synovium injected with mBSA were significantly higher than those in the controls. In some antigen-challenged synovia, increased gene expression of IL-6 was observed. By contrast, expression of the other genes showed no consistent changes between synovia from knees with or without antigen challenge. To determine a definitive role for eosinophils in AIA, we used eosinophil-deficient ΔdblGATA mice for the antigen challenge. We found that the severity scores of arthritis in ΔdblGATA mice were milder than those in WT mice. To investigate whether eosinophils are involved in the adaptive immunity associated with AIA, we analyzed serum IgG and lymph node cell proliferation from both WT and ΔdblGATA mice. This revealed that the anti-mBSA IgG levels were similar in the two strains and that mBSAspecific lymph node cell proliferation in ΔdblGATA mice was impaired. Together, these data indicate that eosinophils play roles in the support of antigen-specific T cell growth responses, and promotion of arthritis. doi：10.11482/KMJ-E40（1）13 (Accepted on October 10, 2013)