Institute for Immunobiology and Department of Immunology, Shanghai Medical College of Fudan University, Shanghai, China.
Lupus. 2012 Apr;21(5):508-16. doi: 10.1177/0961203311434940. Epub 2012 Feb 2.
Our previous study demonstrated that activated lymphocyte derived DNA (ALD-DNA) could function as an autoantigen to induce production of anti-double-stranded DNA (anti-dsDNA) antibodies in syngeneic BALB/c mice. Here we carefully evaluated the potential role of T cells in the induction of anti-dsDNA antibody. We demonstrated that ALD-DNA could effectively induce production of anti-dsDNA antibodies in vivo and in vitro. In contrast, ALD-DNA could not induce the generation of anti-dsDNA antibodies in nude mice. We further showed that in vivo depletion of CD3(+) T cells blocked the induction of anti-dsDNA antibodies in BALB/c mice. Notably, we demonstrated that CD4(+) but not CD8(+) T cells conferred ALD-DNA to induce anti-dsDNA antibodies. Finally, we demonstrated that adoptive transfer of CD4(+) T cells could rescue ALD-DNA induced anti-dsDNA antibodies in nude mice. Our results suggested that T helper cells were required for ALD-DNA to induce anti-dsDNA antibodies. These findings could further our understanding about the immunogenic properties of DNA and throw new light on SLE pathogenesis.
我们之前的研究表明激活的淋巴细胞衍生 DNA(ALD-DNA)可以作为自身抗原,在同基因 BALB/c 小鼠中诱导产生抗双链 DNA(anti-dsDNA)抗体。在这里,我们仔细评估了 T 细胞在诱导抗 dsDNA 抗体中的潜在作用。我们证明了 ALD-DNA 可以在体内和体外有效地诱导抗 dsDNA 抗体的产生。相比之下,ALD-DNA 不能诱导裸鼠产生抗 dsDNA 抗体。我们进一步表明,体内耗尽 CD3(+) T 细胞会阻断 BALB/c 小鼠中抗 dsDNA 抗体的诱导。值得注意的是,我们证明了 CD4(+) T 细胞而不是 CD8(+) T 细胞赋予 ALD-DNA 诱导抗 dsDNA 抗体的能力。最后,我们证明了过继转移 CD4(+) T 细胞可以挽救裸鼠中 ALD-DNA 诱导的抗 dsDNA 抗体。我们的结果表明,辅助性 T 细胞是 ALD-DNA 诱导抗 dsDNA 抗体所必需的。这些发现可以进一步加深我们对 DNA 免疫原性的理解,并为 SLE 的发病机制提供新的见解。