Goldstein Itamar, Simon Amos J, Ben Horin Shomron, Matzri Sarit, Koltakov Alexander, Langevitz Pnina, Rechavi Gideon, Amariglio Ninette, Bank Ilan
Cancer Research Center and Institute of Hematology, The Chaim Sheba Medical Center, Tel Aviv University, Israel.
Clin Immunol. 2008 Jul;128(1):75-84. doi: 10.1016/j.clim.2008.02.014. Epub 2008 May 5.
VLA-1 integrin expressing T cells are more frequent in inflammatory synovial fluids (SF) compared to peripheral blood. Recent studies suggest that VLA-1 expression mainly marks IFNgamma+ T cells while excluding both IL-4+ and regulatory FoxP3+ T cells. To further characterize the TCR repertoire of the potentially pathogenic VLA-1+ IFNgamma+ T cells, isolated from SF of adult patients with rheumatoid and psoriatic arthritis, we determined the complementarity determining region (CDR)3 spectratypes. Here we show in a cohort of 9 patients that VLA-1+ T cells display a perturbed repertoire that, moreover, differs from that of VLA-1- synovial T cells and even VLA-1+ PB T cells. Importantly, random sequencing of the CDR3 region of the TCR variable beta (BV) 6.1 gene of both VLA-1+ and VLA-1- synovial T cells, in one patient, revealed that their sequences were by and large different (29 out of 33 clones). Thus, our results imply that VLA-1+ T cells that infiltrate into inflamed joints represent a partly distinct and highly oligoclonal population of Th1 cells, probably selected by unique antigens.
与外周血相比,表达VLA - 1整合素的T细胞在炎性滑液(SF)中更为常见。最近的研究表明,VLA - 1的表达主要标记IFNγ + T细胞,同时排除IL - 4 +和调节性FoxP3 + T细胞。为了进一步表征从类风湿性关节炎和银屑病关节炎成年患者的滑液中分离出的潜在致病性VLA - 1 + IFNγ + T细胞的TCR库,我们确定了互补决定区(CDR)3谱型。在此我们在9名患者的队列中表明,VLA - 1 + T细胞表现出紊乱的库,而且与VLA - 1 - 滑膜T细胞甚至VLA - 1 +外周血T细胞的库不同。重要的是,对一名患者的VLA - 1 +和VLA - 1 - 滑膜T细胞的TCR可变β(BV)6.1基因的CDR3区域进行随机测序发现,它们的序列大体上不同(33个克隆中有29个)。因此,我们的结果表明,浸润到炎症关节中的VLA - 1 + T细胞代表了部分独特且高度寡克隆的Th1细胞群体,可能是由独特抗原选择的。