CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.
CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.
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DOI：
10.1371/journal.pone.0045185
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ricciardi-Castagnoli P
中科院分区：
文献类型：
--
作者：
Lim TS;Goh JK;Mortellaro A;Lim CT;Hämmerling GJ;Ricciardi-Castagnoli P
功能性T细胞反应是由T细胞与抗原提呈细胞(APC)，包括树突状细胞(DC)和B细胞之间的物理相互作用而启动的。DC比B细胞更有效地激活T细胞，但人们对DC触发T细胞反应的特殊效力的关键分子机制知之甚少。为了更好地了解物理细胞间相互作用对激活T细胞的APC效应的影响，我们使用单胞力谱来表征和比较DC：T细胞和B：T细胞之间相互作用的机械力。抗原刺激后，DC：T细胞结合物的细胞间相互作用强于B：T细胞。DC诱导的T细胞钙动员水平和IL-2和干扰素γ的产生均高于B细胞，提示细胞间的紧密接触在提供机械稳定的环境以启动T细胞激活中起重要作用。针对表面共刺激分子CD80或CD86的封闭抗体削弱了细胞间的相互作用并抑制了T细胞的激活，突出了CD80/86在调节APC：T细胞相互作用和T细胞功能激活中的放大作用。DC：T细胞和B：T细胞之间相互作用的机械力强度的变化并不完全依赖于CD80/86的不同APC表达，因为即使在CD80和CD86被抑制的情况下，DC在促进与T细胞的强相互作用方面也优于B细胞。这些数据提供了对共刺激分子在调节APC：T细胞相互作用中的作用的机械见解。
Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force spectroscopy to characterize and compare the mechanical forces of interactions between DC:T-cells and B:T-cells. Following antigen stimulation, intercellular interactions of DC:T-cell conjugates were stronger than B:T-cell interactions. DCs induced higher levels of T-cell calcium mobilization and production of IL-2 and IFNγ than were elicited by B-cells, thus suggesting that tight intercellular contacts are important in providing mechanically stable environment to initiate T-cell activation. Blocking antibodies targeting surface co-stimulatory molecules CD80 or CD86 weakened intercellular interactions and dampen T-cell activation, highlighting the amplificatory roles of CD80/86 in regulating APC:T-cell interactions and T-cell functional activation. The variable strength of mechanical forces between DC:T-cells and B:T-cell interactions were not solely dependent on differential APC expression of CD80/86, since DCs were superior to B-cells in promoting strong interactions with T-cells even when CD80 and CD86 were inhibited. These data provide mechanical insights into the effects of co-stimulatory molecules in regulating APC:T-cell interactions.
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影响因子：
5.4
作者：
Brossard, C;Feuillet, V;Trautmann, A
通讯作者：
Trautmann, A
B7-1和B7-2共刺激配体的比较分析：表达和功能。
DOI：
10.1084/jem.180.2.631
发表时间：
1994-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hathcock KS;Laszlo G;Pucillo C;Linsley P;Hodes RJ
通讯作者：
Hodes RJ
DOI：
10.1073/pnas.79.11.3604
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KAPPLER, J;WHITE, J;MARRACK, P
通讯作者：
MARRACK, P
影响因子：
56.9
作者：
FREEMAN, GJ;GRIBBEN, JG;NADLER, LM
通讯作者：
NADLER, LM
影响因子：
64.8
作者：
BRUNET, JF;DENIZOT, F;GOLSTEIN, P
通讯作者：
GOLSTEIN, P