CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation
CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation
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DOI：
10.1189/jlb.1107752
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发表时间：
2008-07-01
影响因子：
5.5
通讯作者：
Nagarkatti, Mitzi
中科院分区：
文献类型：
--
作者：
Hegde, Venkatesh L.;Singh, Narendra P.;Nagarkatti, Mitzi
由于其作为细胞粘附和信号分子的双重作用，CD 44参与几种生物学过程。在同种异体树突状细胞（DC）-T细胞相互作用模型中，我们在这里显示，CD 44在T细胞与成熟而非未成熟DC之间的接触处聚集。此外，CD 44与脂筏共定位在免疫突触（IS）。使用来源于CD 44缺陷小鼠的DC或T细胞，我们观察到DC和T细胞上CD 44的存在对于DC-T细胞紧密缀合物的形成是重要的。然而，DC上的CD 44而不是T细胞的缺陷影响功能性IS，如在突触处的磷酸酪氨酸和蛋白激酶C-θ富集减少所示。此外，CD 44缺陷型DC诱导同种异体T细胞的增殖以及IL-2和IFN-γ产生显著降低。在抗原（OVA）特异性的、使用来自OT-II小鼠的OVA特异性T细胞的同基因DC-T细胞相互作用中也注意到突触处的CD 44极化。认为IS中排除了大分子（如CD 44）。本文的结果首次表明，在同种异体DC和T细胞相互作用期间，CD 44被募集到IS，并在随后的T细胞活化中起重要作用。
CD44 is involved in several biological processes owing to its dual role as a cell adhesion and signaling molecule. In an allogeneic dendritic cell (DC)-T cell interaction model, we show here that CD44 gets clustered at the contact between T cells with mature but not immature DCs. Also, CD44 colocalized with lipid rafts at the immunological synapse (IS). Using DCs or T cells derived from CD44-deficient mice, we observed that the presence of CD44 on DCs and T cells is important for the formation of DC-T cell tight conjugates. However, deficiency of CD44 on DCs but not T cells affected the functional IS, as indicated by decreased phosphotyrosine and protein kinase C-theta enrichment at the synapse. Also, CD44-deficient DCs induced significantly decreased proliferation as well as IL-2 and IFN-gamma production from allogeneic T cells. The polarization of CD44 at the synapse was also noted in an antigen (OVA)-specific, syngeneic DC-T cell interaction using OVA-specific T cells derived from OT-II mice. It was believed that large molecules such as CD44 were excluded from the IS. Results presented here show for the first time that CD44 is recruited to the IS during allogeneic DC and T cell interactions and plays an important role in subsequent T cell activation.