HIV感染中的细胞凋亡

Apoptosis in Human Immunodeficiency Virus Infection

CD4+ T细胞的丢失在HIV感染引起免疫缺陷过程中起着重要作用。但造成CD4+ T细胞丢失的具体机制还不清楚。细胞凋亡可能是CD4+ T细胞丢失的一个重要因素。HIV感染以后 ,病毒蛋白的持续性产出导致免疫系统的持续性激活 ,引起Th1细胞的丢失 ,Th1细胞通过合成Ⅰ型细胞因子 ,抑制淋巴细胞的自发凋亡。另外 ,病毒蛋白或其他因素能够使CD4+ 、CD8+ T细胞和APC转化为凋亡的效应细胞 ,通过Fas/FasL或其他途径引起细胞凋亡。HIV感染人体后凋亡细胞不仅有CD4+ T细胞 ,还包括B细胞、NK细胞、粒细胞、神经细胞和单细胞。凋亡作为机体的自我防护措施 ,在清除感染细胞的同时 ,并没有抑制HIV在单细胞 /巨噬细胞内的复制 ,反而造成大量未感染细胞的凋亡 ,导致对HIV复制的失控 ,发展为严重的免疫缺陷 ,引起AIDS相关的机会性感染。

Human immunodeficiency virus (HIV) infection causes progressive loss of CD4+T cells leading to AIDS.The mechanism of T cells deletion is not clearly understood.Apoptosis may be an important factor for the depletion.After HIV infection,continuous production of viral proteins leads to an unbalanced chronic immune activation,which is responsible for the disappearance of T helper cells primed for type-1 cytokine synthesis,thus contributing to the lack of survival factors which could prevent spontaneous lymphocyte apoptosis.The viral proteins or other factors also leads to the triggering of apoptotic programs,turning CD4+,CD8+T cells and APC,into effectors of apoptosis through Fas/FasL or other pathways.Many studies have showed that apoptosis may be responsible not only for the progressive loss of CD4+T cells but may be operative in CD8+T cells,B cells,NK cells,granuloblast,nerve cells and monocytes.Conclusively,Apoptosis,being a body self-defence mechanism,can not inhibit the replication and release of HIV in the reservoir of monocytes/macrophage,on the contrary,cause the death of many uninfected cells,which may lead to the lack of control of HIV replication and to the development of severe immune deficiency responsible for the occurrence of opportunistic infections associated with AIDS.