Kaneshima H
HIV Gene Therapy/Pathogenesis Research SyStemix, Inc., Palo Alto, CA 94304, USA.
Int J Hematol. 1996 Jun;63(4):253-64. doi: 10.1016/0925-5710(96)00452-5.
A variety of possible mechanisms for the loss of CD4+ T cells has been proposed, such as direct cytopathic effects by HIV-1 infection, and indirect induction of apoptosis. However, the fundamental picture of major and central pathogenic processes for the decay of immune systems is still missing in understanding the pathogenic mechanisms of HIV-1 infected humans. It is more appropriate to expand our focus onto entire organ systems involved in the development of immune system such as bone marrow and thymus. From the observations in the clinical studies, HIV-1 causes a variety of pathology on the T cell development pathway even from the hematopoietic progenitors and immature thymocytes, which should have a substantial impact on the failure of T cell homeostasis in the periphery. The SCID-hu mouse constructed by surgical implantation of human fetal hemato-lymphoid organs into the immunodeficient mouse has been used for the experimental evaluation of various parameters associated with HIV-1 infection and hematosuppression. Given the apparently normal structure and function of the human implants, the SCID-hu bone and Thy/Liv mice would appear to be potentially reliable models for the analysis of human physiology and patho-physiology.
关于CD4+T细胞丧失的多种可能机制已被提出，例如HIV-1感染导致的直接细胞病变效应以及间接诱导的细胞凋亡。然而，在理解HIV-1感染人类的致病机制方面，免疫系统衰退的主要和核心致病过程的基本情况仍不清楚。将我们的关注点扩展到参与免疫系统发育的整个器官系统，如骨髓和胸腺，会更为恰当。从临床研究的观察结果来看，即使从造血祖细胞和未成熟胸腺细胞开始，HIV-1在T细胞发育途径上也会引发多种病理变化，这对周围T细胞稳态的失衡应该会产生重大影响。通过将人类胎儿血液淋巴器官手术植入免疫缺陷小鼠构建的SCID-hu小鼠，已被用于对与HIV-1感染和血液抑制相关的各种参数进行实验评估。鉴于人类植入物的结构和功能明显正常，SCID-hu骨和Thy/Liv小鼠似乎有可能成为分析人类生理学和病理生理学的可靠模型。
