Characterizing the dynamics of CD4+ T cell priming within a lymph node.
Characterizing the dynamics of CD4+ T cell priming within a lymph node.
复制标题
DOI：
10.4049/jimmunol.0903117
复制
发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Kirschner DE
中科院分区：
文献类型：
--
作者：
Linderman JJ;Riggs T;Pande M;Miller M;Marino S;Kirschner DE
在感染或免疫后产生适应性免疫需要携带抗原的树突状细胞（DC）和稀有同源T细胞之间在淋巴结（LN）T区内的物理相互作用。关于DC-CD 4 + T细胞相互作用导致引发的动力学仍然存在许多基本问题。例如，尚不清楚引发的CD 4 + T细胞的产生如何与同源T细胞、携带抗原的DC的数量或DC上的肽-MHCII水平相关。为了解决这些问题，我们开发了一个基于代理的LN模型，以检查同源T细胞频率，DC密度，DC-T相互作用的特征参数和致敏T细胞的输出之间的关系。我们发现致敏的CD 4 + T细胞的输出与同源频率线性相关，但与感染期间存在的携带抗原的DC的数量非线性相关。这解决了双光子显微镜研究的适用性，以了解实际的感染动力学，因为这些类型的实验增加同源频率的数量级相比，生理水平。我们发现单个DC表面上的肽-MHCII的量与LN中存在的携带抗原的DC的数量之间存在权衡，这有助于产生引发的CD 4 + T细胞。有趣的是，pMHCII半衰期在决定CD 4 + T细胞引发中起次要作用，尽管仍然显著，与已经提出的用于CD 8 + T细胞引发的主要作用不同。最后，我们确定了几种病原体靶向机制，如果改变其效率，可以显着影响引发的CD 4 + T细胞的产生。
Generating adaptive immunity after infection or immunization requires physical interaction within a lymph node (LN) T-zone between antigen-bearing dendritic cells (DCs) and rare cognate T cells. Many fundamental questions remain regarding the dynamics of DC-CD4+ T cell interactions leading to priming. For example, it is not known how the production of primed CD4+ T cells relates to the numbers of cognate T cells, antigen-bearing DCs, or peptide-MHCII level on the DC. To address these questions, we developed an agent-based model of a LN to examine the relationships among cognate T cell frequency, DC density, parameters characterizing DC-T interactions and the output of primed T cells. We found that the output of primed CD4+ T cells is linearly related to cognate frequency, but non-linearly related to the number of antigen-bearing DCs present during infection. This addresses the applicability of two photon microscopy studies to understanding actual infection dynamics, as these types of experiments increase the cognate frequency by orders of magnitude as compared to physiologic levels. We found a trade-off between the quantity of peptide-MHCII on the surface of individual DCs and number of antigen-bearing DCs present in the LN in contributing to the production of primed CD4+ T cells. Interestingly, pMHCII half-life plays a minor, although still significant, role in determining CD4+ T cell priming, unlike the primary role that has been suggested for CD8+ T cell priming. Finally, we identify several pathogen-targeted mechanisms that, if altered in their efficiency, can significantly effect the generation of primed CD4+ T cells.
登录
查看更多内容
DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
2
作者：
Beauchemin, C;Samuel, J;Tuszynski, J
通讯作者：
Tuszynski, J
影响因子：
5.4
作者：
BEKKHOUCHA, F;NAQUET, P;PIERRES, M
通讯作者：
PIERRES, M
影响因子：
6.4
作者：
Carreno, Leandro J.;Bueno, Susan M.;Kalergis, Alexis M.
通讯作者：
Kalergis, Alexis M.
DOI：
10.1084/jem.20081160
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Figge MT;Garin A;Gunzer M;Kosco-Vilbois M;Toellner KM;Meyer-Hermann M
通讯作者：
Meyer-Hermann M