Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse.
Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse.
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DOI：
10.1038/cmi.2010.9
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发表时间：
2010-05
影响因子：
24.1
通讯作者：
中科院分区：
文献类型：
--
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已知树突状细胞（DC）产生的透明质酸（HA）促进抗原呈递并增强T细胞活化和增殖。我们假设，细胞周HA可以作为细胞间的“胶水”直接介导T细胞- DC结合。使用原代人细胞，我们观察到T细胞和DC之间的HA依赖性结合，其在用阻断HA合成的试剂4-甲基伞形酮（4-MU）预处理DC后被废除。此外，T细胞通过T细胞衍生的细胞因子以TH亚群特异性方式调节DC的HA产生，如通过观察到来自TH 1而不是TH 2克隆的细胞培养物上清液促进HA产生所证明的。在加入外源性TH 1细胞因子IL-2、IFNg和TNFα后观察到类似的作用。决定该系统中DC-T-细胞结合程度的关键因素是DC接受的预处理的性质和它们合成HA的能力，因为用莫能菌素预处理的T-细胞克隆被添加以阻断细胞因子分泌，等同地结合，而不管它们的TH亚群。这些数据支持前馈回路的存在，其中T细胞细胞因子影响HA的DC产生，这反过来影响DC-T细胞结合的程度。我们还记录了HA在T细胞和APC之间的免疫突触处以及被认为在抗原呈递中重要的树突状过程上的局灶性沉积物的存在。这些数据指出HA在免疫突触处的DC -T细胞相互作用中的关键作用。
Hyaluronan (HA) production by dendritic cells (DC) is known to promote antigen presentation and to augment T-cell activation and proliferation. We hypothesized that pericellular HA can function as intercellular “glue” directly mediating T-cell - DC binding. Using primary human cells, we observed HA-dependant binding between T-cells and DC which was abrogated upon pre-treatment of the DC with 4-methylumbelliferone (4-MU), an agent which blocks HA synthesis. Furthermore, T-cells regulate HA production by DC via T-cell derived cytokines in a TH subset–specific manner, as demonstrated by the observation that cell culture supernatants from TH1 but not TH2 clones promote HA production. Similar effects were seen upon the addition of exogenous TH1 cytokines IL-2, IFNg and TNFα. The critical factor which determined the extent of DC - T-cell binding in this system was the nature of the pre-treatment the DC received and their capacity to synthesize HA, as T-cell clones which were pretreated with monensin, added to block cytokine secretion, bound equivalently, irrespective of their TH subset. These data support the existence of a feed-forward loop wherein T-cell cytokines influence DC production of HA which in turn affects the extent of DC-T-cell binding. We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation. These data point to a pivotal role for HA in DC – T-cell interactions at the immune synapse.
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DOI：
10.1098/rstb.1974.0015
发表时间：
1974-01-01
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
ITO, S
通讯作者：
ITO, S
影响因子：
5.5
作者：
Hegde, Venkatesh L.;Singh, Narendra P.;Nagarkatti, Mitzi
通讯作者：
Nagarkatti, Mitzi
影响因子：
6
作者：
Chenevier-Gobeaux, C;Morin-Robinet, S;Borderie, D
通讯作者：
Borderie, D
影响因子：
4.8
作者：
Kakizaki, I;Kojima, K;Itano, N
通讯作者：
Itano, N
影响因子：
56.9
作者：
Grakoui, A;Bromley, SK;Dustin, ML
通讯作者：
Dustin, ML