Ofosu-Appiah W, Aiello V, Sfeir G, Viti D
Department of immunology, Masonic Medical-Research Laboratory, Utica, NY 13501, USA.
J Autoimmun. 1996 Oct;9(5):617-27. doi: 10.1006/jaut.1996.0081.
Autoantigen-reactive T cells might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Autoantigen-reactive T cell clones were generated from spleens of NZB x NZW F1 (BWF1) and normal control BALB/c mice with interleukin-2 (IL-2), a procedure that selects for in vivo activated antigen-reactive T cells. The antigen-specificity of the T cell clones was tested by using a panel of candidate autoantigens. The T cell clones from BWF1 mice but not those from BALB/c mice proliferated against heparan sulfate, the major glycosaminoglycan of glomerular basement membrane. None of the clones proliferated against dsDNA or cardiolipin. All the heparan sulfate-reactive T cell clones had the ability to selectively augment the production of IgG anti-dsDNA autoantibodies. When cultured with either heparan sulfate or Concanavalin A, the T cell clones produced high levels of IL-4 and IL-5 with no detectable IL-2 or IFN-gamma. In contrast, T cell clones derived from BALB/c mice augmented the production of total polyclonal IgG but not the production of anti-dsDNA antibodies. These studies indicate the existence of heparan sulfate-reactive T cells in BWF1 mice. Characterization of heparan sulfate-reactive T cells that could selectively augment anti-dsDNA production will permit the design of targeted and antigen-specific therapy.
自身抗原反应性T细胞可能在系统性红斑狼疮（SLE）的发病机制中起重要作用。用白细胞介素-2（IL-2）从NZB×NZW F1（BWF1）小鼠和正常对照BALB/c小鼠的脾脏中产生自身抗原反应性T细胞克隆，该过程可筛选出体内活化的抗原反应性T细胞。通过使用一组候选自身抗原测试T细胞克隆的抗原特异性。来自BWF1小鼠的T细胞克隆而非来自BALB/c小鼠的T细胞克隆针对硫酸乙酰肝素（肾小球基底膜的主要糖胺聚糖）发生增殖。没有克隆针对双链DNA或心磷脂发生增殖。所有硫酸乙酰肝素反应性T细胞克隆都有选择性增加抗双链DNA自身抗体产生的能力。当与硫酸乙酰肝素或伴刀豆球蛋白A一起培养时，T细胞克隆产生高水平的IL-4和IL-5，未检测到IL-2或干扰素-γ。相比之下，来自BALB/c小鼠的T细胞克隆增加总多克隆IgG的产生，但不增加抗双链DNA抗体的产生。这些研究表明BWF1小鼠中存在硫酸乙酰肝素反应性T细胞。对能够选择性增加抗双链DNA产生的硫酸乙酰肝素反应性T细胞进行表征，将有助于设计靶向性和抗原特异性疗法。
