Fischer A C, Hess A D
Bone Marrow Transplantation Program, Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Exp Med. 1990 Jul 1;172(1):85-94. doi: 10.1084/jem.172.1.85.
The present studies have evaluated the effect of age on the induction of syngeneic graft-versus-host disease (SGVHD) after syngeneic bone marrow transplantation (BMT) and cyclosporine (CsA) therapy. The results clearly document an inverse correlation of age with the incidence of SGVHD. Virtually a 100% incidence of SGVHD occurs in Lewis rats when syngeneic BMT and CsA therapy are started when the animals are 4 wk of age. Thereafter, there is a dramatic decline in the incidence of SGVHD with the increasing age of the animals. Although the age of the recipient was important, the most significant effect was the age of the marrow donor. Marrow from animals 6 mo of age was virtually incapable of eliciting SGVHD after BMT and CsA therapy. Furthermore, mixing the marrow from mature and immature animals resulted in a decreased incidence of SGVHD, implicating a regulatory effect present in the marrow from older rats. This regulatory effect was due to the presence of mature T cells in the marrow from animals 6 mo of age. Despite the fact that marrow from young animals possesses mature T lymphocytes, this regulatory activity was absent, suggesting that the host resistance mediated by T lymphocytes develops as the animal ages. These data further implicate the importance of a host resistance mechanism in preventing the induction of SGVHD with CsA, which appears to be mediated by the clonal inactivation of autoreactive cells.
目前的研究评估了年龄对同基因骨髓移植（BMT）和环孢素（CsA）治疗后同基因移植物抗宿主病（SGVHD）诱导的影响。结果清楚地证明了年龄与SGVHD发病率呈负相关。当在4周龄的动物中开始进行同基因BMT和CsA治疗时，Lewis大鼠中SGVHD的发病率几乎为100%。此后，随着动物年龄的增加，SGVHD的发病率急剧下降。尽管受体的年龄很重要，但最显著的影响是骨髓供体的年龄。6月龄动物的骨髓在BMT和CsA治疗后几乎无法引发SGVHD。此外，将成熟和未成熟动物的骨髓混合会导致SGVHD发病率降低，这表明老年大鼠骨髓中存在调节作用。这种调节作用是由于6月龄动物骨髓中存在成熟T细胞。尽管幼龄动物的骨髓中含有成熟的T淋巴细胞，但这种调节活性并不存在，这表明T淋巴细胞介导的宿主抵抗力随着动物年龄的增长而发展。这些数据进一步表明宿主抵抗机制在预防CsA诱导的SGVHD中的重要性，这似乎是由自身反应性细胞的克隆失活介导的。
