T cell receptor V beta usage in HLA-DQ6αβ8αβ mice displaying spontaneous polyarthritis (137.31)

Abstract

Abstract Spontaneous polyarthritis (SP), an autoimmune disease that develops spontaneously in HLA-DQ6 αβ8aαβ transgenic (tg) mice, is characterized by lymphocyte infiltration in joints leading to chronic polyarthritis in the extremities similar to human rheumatoid arthritis. We examine here the CD4 T cell receptor (TCR) expression in the DQ6/8 tg mice during SP. CD4 T cells were isolated from the lymph nodes of arthritic and non-arthritic DQ6/8 tg mice at various time points, phenotyped via flow cytometry with V beta usage characterized in the CD4+CD25+ T cell population. Preferential usage of V β8.2 was increased from 9% in 2 month naïve mice to 15% in 4 month old and 20% by 8mo old arthritic mice. V β17 expressing T cells also increased from 0.02% in 2 month naïve mice to 2.8% in 4 month old arthritic mice. This is consistent with other studies that have indicated an association of Vβ8.2 TCR in the Experimental Autoimmune Encephalomyelitis and collagen-induced arthritis models. These results support our hypothesis that activated CD4 T cells expressing Vβ8.2 TCR are the predominantly pathogenic; autoreactive T cells involved in SP. Selective depletion of these T cells using anti-Vβ8.2 antibodies will confirm their involvement. Application of such strategies of immune intervention can be helpful in humans to control or reduce the disease progression in the stages of disease initiation. The study was supported by NIH-NIAMS AR45657