Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as well as CD4+ 8- thymocytes and invariant NKT cells but not in Treg cells.
Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as well as CD4+ 8- thymocytes and invariant NKT cells but not in Treg cells.
复制标题
DOI：
10.1371/journal.pone.0031296
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Parker DC
中科院分区：
文献类型：
--
作者：
Koguchi Y;Buenafe AC;Thauland TJ;Gardell JL;Bivins-Smith ER;Jacoby DB;Slifka MK;Parker DC
CD40L 对于适应性免疫反应的发展至关重要。通常认为 CD4+ T 细胞中的 CD40L 表达受到转录调节，并由抗原识别后的新 mRNA 制成。然而，成像研究表明，体内效应 CD4+ T 细胞和 APC 之间的大多数同源相互作用都太短，无法从头合成 CD40L。我们之前表明，Th1 效应细胞和记忆细胞将预先形成的 CD40L (pCD40L) 储存在溶酶体区室中，并在抗原刺激后立即将其动员到质膜上，这表明已启动的 CD4+ T 细胞可能在短暂相遇期间使用 pCD40L 来激活 APC。事实上，我们最近的研究表明 pCD40L 足以介导同源 B 细胞的选择性激活并在体外触发 DC 激活。在这项研究中，我们发现 pCD40L 存在于淋巴细胞性脉络膜脑膜炎病毒感染过程中形成的 Th1 和滤泡辅助 T 细胞、哮喘小鼠气道中的 Th2 细胞以及实验性自身免疫性脑炎 (EAE) 动物 CNS 的 Th17 细胞中。 pCD40L 在天然和诱导的 Treg 细胞中几乎不存在，即使存在严重炎症（例如 EAE 中发生的炎症）。我们还在 CD4 单阳性胸腺细胞和不变 NKT 细胞中发现了 pCD40L 表达。总之，这些结果表明 pCD40L 可能在 T 细胞发育以及意想不到的广谱先天性和适应性免疫反应中发挥作用，同时它在 Treg 细胞中的表达受到抑制，以避免损害其抑制活性。
CD40L is essential for the development of adaptive immune responses. It is generally thought that CD40L expression in CD4+ T cells is regulated transcriptionally and made from new mRNA following antigen recognition. However, imaging studies show that the majority of cognate interactions between effector CD4+ T cells and APCs in vivo are too short to allow de novo CD40L synthesis. We previously showed that Th1 effector and memory cells store preformed CD40L (pCD40L) in lysosomal compartments and mobilize it onto the plasma membrane immediately after antigenic stimulation, suggesting that primed CD4+ T cells may use pCD40L to activate APCs during brief encounters. Indeed, our recent study showed that pCD40L is sufficient to mediate selective activation of cognate B cells and trigger DC activation in vitro. In this study, we show that pCD40L is present in Th1 and follicular helper T cells developed during infection with lymphocytic choriomeningitis virus, Th2 cells in the airway of asthmatic mice, and Th17 cells from the CNS of animals with experimental autoimmune encephalitis (EAE). pCD40L is nearly absent in both natural and induced Treg cells, even in the presence of intense inflammation such as occurs in EAE. We also found pCD40L expression in CD4 single positive thymocytes and invariant NKT cells. Together, these results suggest that pCD40L may function in T cell development as well as an unexpectedly broad spectrum of innate and adaptive immune responses, while its expression in Treg cells is repressed to avoid compromising their suppressive activity.
登录
查看更多内容
影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
DOI：
10.4049/jimmunol.0901689
发表时间：
2010-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bolduc A;Long E;Stapler D;Cascalho M;Tsubata T;Koni PA;Shimoda M
通讯作者：
Shimoda M
影响因子：
4.4
作者：
Clegg, CH;Rulffes, JT;Hollenbaugh, D
通讯作者：
Hollenbaugh, D
影响因子：
5.4
作者：
BOWEN, F;HALUSKEY, J;QUILL, H
通讯作者：
QUILL, H
DOI：
10.1073/pnas.0700191104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Galli, Grazia;Pittoni, Paola;Abrignani, Sergio
通讯作者：
Abrignani, Sergio