用抗DNA免疫球蛋白共有肽进行体细胞B细胞基因疫苗接种后，（NZB×NZW）F（1）狼疮易感小鼠的肾脏疾病防护

Protection against renal disease in (NZB x NZW)F(1) lupus-prone mice after somatic B cell gene vaccination with anti-DNA immunoglobulin consensus peptide.

作者信息

Ferrera Francesca, Hahn Bevra H, Rizzi Marta, Anderson Marissa, Fitzgerald John, Millo Enrico, Indiveri Francesco, Shi Fu-Dong, Filaci Gilberto, La Cava Antonio

机构信息

David Geffen School of Medicine, University of California, Los Angeles, California, USA.

出版信息

Arthritis Rheum. 2007 Jun;56(6):1945-53. doi: 10.1002/art.22700.

DOI:10.1002/art.22700

PMID:17530718

Abstract

OBJECTIVE

Ig molecules contain epitopes that can induce T cell-mediated immune responses. B cells can process and present such epitopes and activate T cells. The purpose of the present study was to test our hypothesis that T cells that recognize an Ig consensus sequence presented by B cells will modulate lupus-like disease in mice.

METHODS

(NZB x NZW)F(1) (NZB/NZW) lupus mice received somatic B cell gene transfer of a DNA plasmid encoding a consensus sequence of T cell determinants of murine anti-DNA IgG or control plasmids. Treated animals were monitored for the production of antibody, the development of renal disease, and the phenotype, number, and function of T cells.

RESULTS

Treatment of mice with Ig consensus plasmid induced transforming growth factor beta-producing CD8+,CD28- T cells that suppressed the antigen-specific stimulation of CD4+ T cells in a cell-contact-independent manner, reduced antibody production, retarded the development of nephritis, and improved survival. Significantly, adoptive transfer of CD8+,CD28- T cells from protected mice into hypergammaglobulinemic NZB/NZW mice effectively protected the transferred mice from the development of renal disease.

CONCLUSION

Gene expression of anti-DNA Ig consensus sequence induces immunoregulatory T cells that delay the development of lupus nephritis by suppressing hypergammaglobulinemia and renal disease.

摘要

目的

免疫球蛋白（Ig）分子含有可诱导T细胞介导的免疫反应的表位。B细胞能够处理并呈递此类表位，进而激活T细胞。本研究的目的是验证我们的假说，即识别由B细胞呈递的Ig共有序列的T细胞将调节小鼠的狼疮样疾病。

方法

（新西兰黑鼠×新西兰白鼠）F1（NZB/NZW）狼疮小鼠接受了编码鼠抗DNA IgG的T细胞决定簇共有序列的DNA质粒或对照质粒的体细胞B细胞基因转移。对接受治疗的动物监测抗体产生、肾脏疾病发展以及T细胞的表型、数量和功能。

结果

用Ig共有序列质粒治疗小鼠可诱导产生转化生长因子β的CD8⁺、CD28⁻ T细胞，这些细胞以不依赖细胞接触的方式抑制CD4⁺ T细胞的抗原特异性刺激，减少抗体产生，延缓肾炎发展，并提高生存率。重要的是，将来自受保护小鼠的CD8⁺、CD28⁻ T细胞过继转移至高丙种球蛋白血症的NZB/NZW小鼠中，可有效保护被转移小鼠不发生肾脏疾病。