Dang H, Geiser A G, Letterio J J, Nakabayashi T, Kong L, Fernandes G, Talal N
Audie L. Murphy Memorial Veterans Hospital, San Antonio, Texas, USA.
J Immunol. 1995 Sep 15;155(6):3205-12.
Mice bearing the TGF-beta 1 null mutation (-/-) develop lymphoid infiltrates in the heart, lungs, salivary glands, and other organs similar to those seen in the pseudolymphoma of Sjögren's Syndrome. We studied sera from -/- mice and found elevated Ab levels to dsDNA, ssDNA, and Sm ribonucleoprotein. No Abs to SSA/Ro or SSB/La and no IgM rheumatoid factor were found. Serum autoantibodies were predominately IgG and were specific as shown by ELISA inhibition studies. Antinuclear Ab patterns on Western blots varied from one mouse to the next, indicating a random process responsible for the diversity. Wild-type and heterozygote mice had no autoantibodies. Ig glomerular deposits were found in -/- mice, indicating that these autoantibodies may be pathogenic. Treatment of -/- mice with dexamethasone or TGF-beta 1 failed to suppress autoantibody production. These mice represent an overlap combining the autoimmune serology of SLE with the tissue infiltrates of SS. Our results support the concept that TGF-beta 1 is an important naturally occurring immunosuppressive cytokine whose absence can lead to a systemic autoimmune disease.
携带转化生长因子β1基因无效突变（-/-）的小鼠在心脏、肺、唾液腺和其他器官出现淋巴浸润，类似于干燥综合征假性淋巴瘤中所见。我们研究了-/-小鼠的血清，发现其抗双链DNA、单链DNA和Sm核糖核蛋白的抗体水平升高。未发现抗SSA/Ro或SSB/La抗体以及IgM类风湿因子。血清自身抗体主要为IgG，酶联免疫吸附抑制试验表明其具有特异性。蛋白质免疫印迹上的抗核抗体模式在不同小鼠之间有所不同，表明是一个导致多样性的随机过程。野生型和杂合子小鼠没有自身抗体。在-/-小鼠中发现了Ig肾小球沉积物，表明这些自身抗体可能具有致病性。用地塞米松或转化生长因子β1治疗-/-小鼠未能抑制自身抗体的产生。这些小鼠代表了系统性红斑狼疮的自身免疫血清学与干燥综合征的组织浸润的重叠。我们的结果支持这样的概念，即转化生长因子β1是一种重要的天然存在的免疫抑制细胞因子，其缺失可导致全身性自身免疫疾病。
