Ria Francesco, Penitente Romina, De Santis Maria, Nicolò Chiara, Di Sante Gabriele, Orsini Massimiliano, Arzani Dario, Fattorossi Andrea, Battaglia Alessandra, Ferraccioli Gian Franco
Institute of General Pathology, Catholic University, Largo F Vito, Rome, Italy.
Arthritis Res Ther. 2008;10(6):R135. doi: 10.1186/ar2553. Epub 2008 Nov 17.
Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.
We used the CDR3 BV-BJ spectratyping to study the response to human collagen peptide 261-273 in 12 patients with DR4+ rheumatoid arthritis (six at the onset of disease and six during the course of disease) and in five healthy DR4+ relatives.
The collagen-specific T-cell repertoire is quite restricted at the onset of disease, involving approximately 10 rearrangements. Within the studied collagen-specific rearrangements, nearly 75% is shared among patients. Although the size of the repertoire used by control individuals is comparable to that of patients, it is characterized by different T-cell receptors. Part of the antigen-specific T-cell repertoire is spontaneously enriched in synovial fluid. The specific T-cell repertoire in the periphery was modulated by therapy and decreased with the remission of the disease. Failure of immunoscopy to detect this repertoire was not due to suppression of collagen-driven proliferation in vitro by CD4+ CD25+ T cells. Clinical relapse of the disease was associated with the appearance of the original collagen-specific T cells.
The collagen-specific T-cell receptor repertoire in peripheral blood and synovial fluid is restricted to a limited number of rearrangements in rheumatoid arthritis. The majority of the repertoire is shared between patients with early rheumatoid arthritis and it is modulated by therapy.
II型胶原蛋白是维持类风湿性关节炎的自身反应性T细胞的DR4/DR1限制性靶点。本研究的目的是分析类风湿性关节炎发病时及不同阶段的T细胞受体库。
我们使用CDR3 BV-BJ谱型分析来研究12例DR4+类风湿性关节炎患者（6例疾病发作期患者和6例疾病病程中患者）以及5名健康DR4+亲属对人胶原蛋白肽261-273的反应。
疾病发作时，胶原蛋白特异性T细胞受体库相当有限，涉及约10种重排。在所研究的胶原蛋白特异性重排中，近75%在患者之间是共享的。虽然对照个体使用的受体库大小与患者相当，但其特征是T细胞受体不同。部分抗原特异性T细胞受体库在滑液中自发富集。外周血中的特异性T细胞受体库受治疗调节，并随疾病缓解而减少。免疫检测未能检测到该受体库并非由于CD4+CD25+T细胞在体外抑制了胶原蛋白驱动的增殖。疾病的临床复发与原始胶原蛋白特异性T细胞的出现有关。
在类风湿性关节炎中，外周血和滑液中的胶原蛋白特异性T细胞受体库限于有限数量的重排。大多数受体库在早期类风湿性关节炎患者之间共享，并受治疗调节。
