Sardiña E E, Sugiura K, Ikehara S, Good R A
Department of Pediatrics, All Children's Hospital, St. Petersburg, FL 33701.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3218-22. doi: 10.1073/pnas.88.8.3218.
Hematopoietic stem cell defects are thought to be involved in the etiopathogenesis of systemic autoimmune disease. Positively selected, stem cell-enriched populations of wheat germ agglutinin-positive (WGA+) low-density bone marrow and fetal liver cells from normal and autoimmune-prone mice were used to determine whether reciprocal transplantation of stem cells between normal and autoimmune-prone mice inhibits or causes development of autoimmune disease. NZB recipients of DBA/2 stem cell populations analyzed greater than 100 days after bone marrow or fetal liver cell transplantation showed decreased levels of anti-DNA antibodies and decreased glomerular lesions when compared with nontreated NZB mice or NZB recipients of NZB stem cell preparations. Female DBA/2 recipients of WGA+ NZB bone marrow cell or fetal liver cell transplants exhibited elevated serum autoantibody levels and developed glomerular lesions characteristic of NZB mice when analyzed greater than 100 days after transplantation. These pathological disturbances were not observed in DBA/2 recipients of DBA/2 stem cell preparations. The data indicate that WGA+ stem cells from autoimmune-prone NZB mice contain the genetic defects responsible for the development of systemic autoimmune disease.
造血干细胞缺陷被认为与系统性自身免疫性疾病的发病机制有关。从正常和易患自身免疫性疾病的小鼠中,选取经阳性选择的富含干细胞的麦胚凝集素阳性(WGA+)低密度骨髓细胞群和胎肝细胞群,以确定正常小鼠和易患自身免疫性疾病的小鼠之间相互移植干细胞是否会抑制或引发自身免疫性疾病的发展。对骨髓或胎肝细胞移植后100多天进行分析,结果显示,与未治疗的NZB小鼠或接受NZB干细胞制剂的NZB受体相比,接受DBA/2干细胞群的NZB受体抗DNA抗体水平降低,肾小球病变减少。移植后100多天进行分析时,接受WGA+ NZB骨髓细胞或胎肝细胞移植的雌性DBA/2受体血清自身抗体水平升高,并出现了NZB小鼠特有的肾小球病变。在接受DBA/2干细胞制剂的DBA/2受体中未观察到这些病理紊乱。数据表明,来自易患自身免疫性疾病的NZB小鼠的WGA+干细胞含有导致系统性自身免疫性疾病发展的遗传缺陷。