Hattori N, Kuwana M, Kaburaki J, Mimori T, Ikeda Y, Kawakami Y
Keio University School of Medicine, Tokyo, Japan.
Arthritis Rheum. 2000 Jan;43(1):65-75. doi: 10.1002/1529-0131(200001)43:1<65::AID-ANR9>3.0.CO;2-I.
To identify the T cells responsive to beta2-glycoprotein I (beta2GPI) that mediate antiphospholipid antibody production in patients with antiphospholipid syndrome (APS).
In vitro proliferative responses and anti-beta2GPI antibody production induced by beta2GPI were examined in peripheral blood mononuclear cell (PBMC) cultures from 12 APS patients, 13 systemic lupus erythematosus patients without APS, and 12 healthy donors.
Peripheral blood T cells from all subjects failed to respond to beta2GPI in its native form. In contrast, reduced beta2GPI was able to stimulate T cells not only from all 12 patients with anti-beta2GPI antibodies, but also from 10 of 25 individuals without anti-beta2GPI antibodies. The specificity of the responses to beta2GPI was confirmed by activation of the reduced beta2GPI-primed T cells by recombinant beta2GPI in secondary cultures. Characterization of the T cell response induced by beta2GPI revealed that the response was associated with the presence of the DR53-associated alleles, the responding T cells were CD4+ and restricted by HLA class II, and antigenic peptides were located in domains IV and/or V. Anti-beta2GPI antibody production was induced specifically in anti-beta2GPI antibody-positive patients, in PBMC cultures with reduced beta2GPI. Anti-beta2GPI antibodies produced in vitro recognized beta2GPI immobilized with cardiolipin or beta2GPI coated on "high-binding" polystyrene plates.
These results strongly suggest that CD4+ and HLA class II-restricted T cells responsive to beta2GPI are involved in the production of antiphospholipid antibodies in APS patients.
鉴定抗磷脂综合征（APS）患者中对β2糖蛋白I（β2GPI）产生应答并介导抗磷脂抗体产生的T细胞。
检测了12例APS患者、13例无APS的系统性红斑狼疮患者和12名健康供者外周血单个核细胞（PBMC）培养物中β2GPI诱导的体外增殖反应和抗β2GPI抗体产生情况。
所有受试者的外周血T细胞对天然形式的β2GPI均无反应。相比之下，还原型β2GPI不仅能够刺激所有12例抗β2GPI抗体阳性患者的T细胞，还能刺激25例无抗β2GPI抗体个体中的10例的T细胞。在二次培养中，重组β2GPI激活还原型β2GPI致敏的T细胞，证实了对β2GPI反应的特异性。对β2GPI诱导的T细胞反应的特征分析显示，该反应与DR53相关等位基因的存在有关，反应性T细胞为CD4 + 且受HLA II类分子限制，抗原肽位于结构域IV和/或V。在含有还原型β2GPI的PBMC培养物中，抗β2GPI抗体阳性患者特异性诱导产生抗β2GPI抗体。体外产生的抗β2GPI抗体可识别用心磷脂固定的β2GPI或包被在“高结合”聚苯乙烯板上的β2GPI。
这些结果强烈提示，对β2GPI产生应答的CD4 + 和HLA II类分子限制的T细胞参与了APS患者抗磷脂抗体的产生。
