IL-2 Regulates Expansion of CD4+ T Cell Populations by Affecting Cell Death: Insights from Modeling CFSE Data1
IL-2 Regulates Expansion of CD4+ T Cell Populations by Affecting Cell Death: Insights from Modeling CFSE Data1
复制标题
IL-2 通过影响细胞死亡来调节 CD4 T 细胞群的扩增：CFSE 数据建模的见解1
作者：
V. V. Ganusov;D. Milutinović;R. D. de Boer
普遍认为IL-2影响体外和体内T细胞群体的动力学。然而，哪些细胞分裂和/或死亡的参数受IL-2的影响还不清楚。为了更好地了解IL-2如何影响T细胞的群体动力学的潜在途径，我们分析了CFSE标记的多克隆CD 4 + T淋巴细胞在不同浓度的外源性IL-2抗CD 3刺激后的体外动力学数据。从CFSE去标记实验中推断细胞分裂和死亡率并不简单，需要使用数学模型。我们发现，为了充分描述在低浓度的外源性IL-2的T细胞的动态，分裂细胞的死亡率必须随着细胞分裂次数的增加而增加。IL-2几乎不影响平均分裂间期。在低IL-2浓度下，1）较少的细胞被募集到应答中并成功完成其第一次分裂; 2）细胞分裂的随机性增加;和3）死亡率随分裂次数增加而增加的速率增加。总之，我们的数学重新解释表明，IL-2对初始CD 4 + T细胞的体外动力学的主要影响是通过影响细胞死亡率而不是通过改变细胞分裂率来发生的。
It is generally accepted that IL-2 influences the dynamics of populations of T cells in vitro and in vivo. However, which parameters for cell division and/or death are affected by IL-2 is not well understood. To get better insights into the potential ways of how IL-2 may influence the population dynamics of T cells, we analyze data on the dynamics of CFSE-labeled polyclonal CD4+ T lymphocytes in vitro after anti-CD3 stimulation at different concentrations of exogenous IL-2. Inferring cell division and death rates from CFSE-delabeling experiments is not straightforward and requires the use of mathematical models. We find that to adequately describe the dynamics of T cells at low concentrations of exogenous IL-2, the death rate of divided cells has to increase with the number of divisions cells have undergone. IL-2 hardly affects the average interdivision time. At low IL-2 concentrations 1) fewer cells are recruited into the response and successfully complete their first division; 2) the stochasticity of cell division is increased; and 3) the rate, at which the death rate increases with the division number, increases. Summarizing, our mathematical reinterpretation suggests that the main effect of IL-2 on the in vitro dynamics of naive CD4+ T cells occurs by affecting the rate of cell death and not by changing the rate of cell division.
影响因子：
56.9
作者：
SMITH, KA
通讯作者：
SMITH, KA
影响因子：
56.9
作者：
CANTRELL, DA;SMITH, KA
通讯作者：
SMITH, KA
影响因子：
56.9
作者：
Opferman, JT;Ober, BT;Ashton-Rickardt, PG
通讯作者：
Ashton-Rickardt, PG