Behar S M, Roy C, Lederer J, Fraser P, Brenner M B
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 1998 Mar;41(3):498-506. doi: 10.1002/1529-0131(199803)41:3<498::AID-ART16>3.0.CO;2-4.
Previously, we showed that 15-20% of patients with rheumatoid arthritis (RA) have oligoclonal expansions of peripheral blood CD8+ T cells expressing T cell receptors encoded by the V(alpha)12 (AV12S1) gene. To better understand the significance of these expansions, the present study was undertaken to determine their specificity.
We cloned and characterized V(alpha)12+,CD8+ T cells from the peripheral blood of 1 RA patient with a clonal expansion of these T cells.
The T cell clones were autoreactive since they recognized autologous, but not allogeneic, antigen-presenting cells. Upon activation, these T cells secreted interleukin-4 and interleukin-10. The autoreactive T cell clones were class I major histocompatibility complex (MHC) restricted, by either HLA-B60 or HLA-Cw3.
A large population of class I MHC-restricted CD8+ T cells in a patient with RA is clonally expanded and autoreactive. These cells define a novel immune aberration in RA and provide a tool for defining the autoantigens that activate expanded T cell populations in vivo.
此前,我们发现15%至20%的类风湿关节炎(RA)患者外周血CD8⁺T细胞存在寡克隆扩增,这些T细胞表达由V(α)12(AV12S1)基因编码的T细胞受体。为了更好地理解这些扩增的意义,本研究旨在确定其特异性。
我们从1例T细胞克隆扩增的RA患者外周血中克隆并鉴定了V(α)12⁺、CD8⁺T细胞。
这些T细胞克隆具有自身反应性,因为它们识别自体而非异体抗原呈递细胞。激活后,这些T细胞分泌白细胞介素-4和白细胞介素-10。这些自身反应性T细胞克隆受I类主要组织相容性复合体(MHC)限制,限制因素为HLA - B60或HLA - Cw3。
1例RA患者中大量受I类MHC限制的CD8⁺T细胞发生克隆扩增并具有自身反应性。这些细胞定义了RA中一种新的免疫异常,并为确定体内激活扩增T细胞群体的自身抗原提供了一种工具。