Mackall C L, Gress R E
Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892-1928, USA.
Immunol Rev. 1997 Jun;157:61-72. doi: 10.1111/j.1600-065x.1997.tb00974.x.
Much of our understanding of the immunobiology of bone marrow transplantation (BMT) has come from studies in young adult mice reconstituted with T-cell-depleted bone marrow after lethal irradiation. Recent evidence indicates, however, that the applicability of conclusions drawn from this model to human BMT may be limited. While mice retain essentially normal thymic function well past sexual maturity, humans show significant age-related declines in thymic function relatively early in life. Therefore, thymic-deficient mice may provide a more accurate model for study of the immunobiology of BMT. T-cell regeneration in thymic-deficient mice occurs primarily via antigen-driven expansion of mature peripheral T cells resulting in limited immune competence due to quantitative deficiencies in T-cell number and severe restriction in the diversity of the regenerated T-cell receptor (TCR) repertoire. Similarly, immune reconstitution in adult humans after BMT is marked by quantitative T-cell deficiencies, especially in the CD4+ subset, and loss of TCR diversity. Taken together, prevailing evidence suggests that thymic function is suboptimal in most BMT recipients, and that thymic-independent pathways of T-cell regeneration are generally limited in their ability to restore host immune competence. New strategies to enhance thymic function in man after BMT would hold great therapeutic potential.
我们对骨髓移植（BMT）免疫生物学的许多理解都来自于对成年小鼠的研究，这些小鼠在接受致死性照射后用去除T细胞的骨髓进行重建。然而，最近的证据表明，从这个模型得出的结论应用于人类BMT时可能存在局限性。虽然小鼠在性成熟后很长时间内仍保持基本正常的胸腺功能，但人类在生命相对早期就出现了与年龄相关的胸腺功能显著下降。因此，胸腺缺陷小鼠可能为研究BMT的免疫生物学提供更准确的模型。胸腺缺陷小鼠中的T细胞再生主要通过成熟外周T细胞的抗原驱动扩增发生，由于T细胞数量的定量缺陷和再生T细胞受体（TCR）库多样性的严重限制，导致免疫能力有限。同样，成年人类BMT后的免疫重建以T细胞数量定量缺陷为特征，尤其是在CD4 +亚群中，并且TCR多样性丧失。综上所述，现有证据表明，大多数BMT受者的胸腺功能欠佳，并且T细胞再生的非胸腺途径在恢复宿主免疫能力方面的能力通常有限。BMT后增强人类胸腺功能的新策略将具有巨大的治疗潜力。
