Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes.

Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes.
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DOI:
10.1084/jem.184.2.569
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发表时间:
1996-08-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Moser B
Moser B
中科院分区:
其他
文献类型:
--
作者:
Loetscher P;Seitz M;Baggiolini M;Moser B

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一些研究表明CC趋化因子吸引T淋巴细胞,CD45RO+,记忆表型细胞被认为是主要的应答者。然而,结果往往是相互矛盾的,淋巴细胞活化和增殖的作用仍然不清楚。利用不同刺激条件下培养的CD45RO+血淋巴细胞,我们研究了趋化性和趋化因子受体的表达。RANTES/MIP-1 α受体(CC- CKR1)和MCP-1受体(CC- ckr2)的表达与向RANTES、MCP-1和其他CC趋化因子的迁移高度相关,并且严格依赖于培养基中IL-2的存在。停用IL-2后,迁移和受体表达迅速下调,再次加入IL-2后,迁移和受体表达完全恢复。IL-2的作用可以被IL-4、IL-10或IL-12部分模仿,但不能被IL-13、IFN γ、IL-1 β、tnf - α或暴露于抗cd3、抗cd28或植物血凝素所模仿。通过TCR/CD3复合物和CD28抗原激活完全应答淋巴细胞实际上具有相反的效果。即使在IL-2存在的情况下,它也能迅速下调受体的表达和随之而来的迁移。与对CC趋化因子受体的影响相反,IL-2刺激CD45RO+ T淋巴细胞既没有诱导CXC趋化因子受体IL8-R1和IL8-R2的表达,也没有对IL-8的趋化性。IL-2在淋巴细胞CC趋化因子反应中的突出作用表明,IL-2介导的扩增是抗原活化T细胞募集到免疫和炎症反应部位的先决条件。
Several studies have shown that CC chemokines attract T lymphocytes, and that CD45RO+, memory phenotype cells are considered to be the main responders. The results, however, have often been contradictory and the role of lymphocyte activation and proliferation has remained unclear. Using CD45RO+ blood lymphocytes cultured under different stimulatory conditions, we have now studied chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP-1 alpha receptor (CC- CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly dependent on the presence of IL-2 in the culture medium. Migration and receptor expression were rapidly downregulated when IL-2 was withdrawn, but were fully restored when IL-2 was added again. The effect of IL-2 could be partially mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF-alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen actually had the opposite effect. It rapidly downregulated receptor expression and consequent migration even in the presence of IL-2. In contrast to the effects on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the recruitment of antigen-activated T cells into sites of immune and inflammatory reactions.
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期刊: BIOCHEMISTRY
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发表时间: 1994-10-01
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影响因子: 4.8
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