Helper-dependent vs. helper-independent CTL responses in HIV infection: Implications for drug therapy and resistance
Helper-dependent vs. helper-independent CTL responses in HIV infection: Implications for drug therapy and resistance
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DOI：
10.1006/jtbi.2001.2426
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发表时间：
2001-12-07
影响因子：
2
通讯作者：
Wodarz, D
中科院分区：
文献类型：
--
作者：
Wodarz, D
HIV 感染患者的临床数据以及理论研究表明，在存在和不存在 CD4 细胞帮助的情况下，CTL 反应有本质上的不同。在有帮助的情况下，尽管抗原负荷非常低，CTL 反应仍能维持，并长期控制感染。在缺乏特异性辅助细胞反应的情况下，CTL 需要维持高抗原负荷，在低水平抗原下寿命较短，并且不能长期控制感染。本文描述了分析 HIV 感染中辅助依赖性和非辅助 CTL 动态的数学模型，特别关注慢性感染药物治疗期间的动态。理论表明，病毒传播速度过快会导致辅助细胞高度损伤，从而促进不依赖于辅助细胞的 CTL 反应的发展，并导致免疫控制受损。与临床发现一致，该模型表明，治疗开始后，CTL 水平会短暂增加，一旦病毒载量被显着抑制，CTL 水平就会下降至较低水平。根据该模型，独立于辅助者的 CTL 的存在可以促进依赖于辅助者的记忆反应的建立。有趣的是，这引发了这样的预测：在 CTL 水平降至阈值以下之前相对较早地停止治疗可以促进免疫控制的改善。讨论了有关治疗时间和持续时间的问题。药物治疗过程中的 CTL 动力学也为治疗过程中耐药菌株出现的原理提供了新的见解。 (C) 2001 年学术出版社。
Clinical data from HIV-infected patients, as well as theoretical studies, suggest that CTL responses in the presence and absence of CD4 cell help are qualitatively different. In the presence of help, CTL responses are maintained despite very low antigenic loads and control the infection in the long term. In the absence of specific helper cell responses, CTL require high antigenic loads to be maintained, are short lived at low levels of antigen, and do not control the infection in the long term. This paper describes mathematical models analysing the dynamics of helper-dependent and helper-independent CTL in HIV infection with special focus on the dynamics during drug therapy in chronic infection. Theory suggests that a fast rate of virus spread results in high degrees of helper cell impairment which promotes the development of helper-independent CTL responses and compromised immunological control. In agreement with clinical findings, the model suggests that upon start of therapy, there is a transient increase in the level of CTL, followed by a decline to low levels once virus load has been significantly suppressed. According to the model, the presence of helper-independent CTL can promote the establishment of a helper-dependent memory response. Interestingly, this gives rise to the prediction that a relatively early stop of therapy, before the level of CTL has fallen below a threshold, can promote improved immunological control. Issues concerning the timing and duration of treatment are discussed. The CTL kinetics during drug therapy also provide new insights into the principles underlying the emergence of drug-resistant strains during the course of treatment. (C) 2001 Academic Press.