Wang B Y, El-Badri N S, Good R A
Department of Pediatrics, University of South Florida, All Children's Hospital, St. Petersburg, FL 33701, USA.
Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12065-9. doi: 10.1073/pnas.94.22.12065.
Transplantations of fully allogeneic, autoimmune-resistant T-cell-depleted marrow (TCDM) plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice were carried out to investigate the ability of the mixed bone marrow transplantation (BMT) to prevent development of autoimmune disease and, at the same time, to reconstitute fully the immunity functions of heavily irradiated BXSB recipients. Male BXSB mice were engrafted with mixed TCDM from both allogeneic, autoimmune-resistant BALB/c mice and syngeneic, autoimmune-prone BXSB mice. BMT with mixed TCDM from both resistant and susceptible strains of mice (mixed BMT) prolonged the median life span and inhibited development of glomerulonephritis in BXSB mice. BMT with mixed TCDM also prevented the formation of anti-DNA antibodies that is typically observed in male mice of this strain. Moreover, mixed BMT reconstituted primary antibody production in BXSB recipients, so that no annoying immunodeficiencies that are regularly observed in fully allogeneic chimeras were present in the recipient of the mixed TCDM. These findings indicate that transplanting allogeneic, autoimmune-resistant TCDM plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice prevents development of autoimmune disease in this strain of mice. In addition, this dual BMT reconstitutes the immunity functions and avoids the immunodeficiencies that occur regularly in fully allogeneic chimeras after total-body irradiation.
将完全异基因、抗自身免疫的去T细胞骨髓(TCDM)与同基因、易患自身免疫的TCDM移植到经致死剂量照射的BXSB小鼠体内,以研究混合骨髓移植(BMT)预防自身免疫性疾病发生的能力,同时完全重建经重度照射的BXSB受体的免疫功能。雄性BXSB小鼠接受来自异基因、抗自身免疫的BALB/c小鼠和同基因、易患自身免疫的BXSB小鼠的混合TCDM移植。用来自抗性和易感小鼠品系的混合TCDM进行BMT(混合BMT)延长了BXSB小鼠的中位寿命并抑制了肾小球肾炎的发展。用混合TCDM进行BMT还可防止在该品系雄性小鼠中通常观察到的抗DNA抗体的形成。此外,混合BMT重建了BXSB受体的初次抗体产生,因此在混合TCDM受体中不存在在完全异基因嵌合体中经常观察到的令人烦恼的免疫缺陷。这些发现表明,将异基因、抗自身免疫的TCDM与同基因、易患自身免疫的TCDM移植到经致死剂量照射的BXSB小鼠体内可预防该品系小鼠自身免疫性疾病的发生。此外,这种双重BMT可重建免疫功能并避免全身照射后在完全异基因嵌合体中经常出现的免疫缺陷。