Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy.

Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy.
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DOI:
10.1186/1471-2172-7-14
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发表时间:
2006-07-07
期刊:
影响因子:
3
通讯作者:
Ransohoff RM
Ransohoff RM
中科院分区:
医学4区
文献类型:
--
作者:
Kivisäkk P;Tucky B;Wei T;Campbell JJ;Ransohoff RM

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循环记忆 T 细胞可分为组织特异性亚群,根据其粘附分子和趋化因子受体的表达,这些亚群在生理免疫监视过程中穿过不同的组织区室。我们推断,已知器官特异性运输决定因素的 CSF T 细胞表达的偏差(富集或缺失)可能表明 T 细胞归巢到蛛网膜下腔可能受到 CNS 特异性粘附分子或趋化因子受体的控制。使用流式细胞术分析非炎症性神经系统疾病患者脑脊液中 CD4+ 记忆 T 细胞的皮肤白细胞抗原 (CLA) 和 CC 趋化因子受体 4(CCR4;与皮肤归巢相关)的表达以及整合素 α4β7 和 CCR9(与肠道归巢相关)的表达。 CSF 含有相似比例的表达 CLA、CCR4、整合素 α4β7 和 CCR9 的 CD4+ 记忆 T 细胞,作为配对的血液样本。这些结果扩展了我们之前的发现,即经历过抗原的 CD4+ 记忆 T 细胞通过脑脊液的流量与其在外周循环中的丰度成比例。此外,皮肤和肠道归巢 CD4+ 记忆 T 细胞可以通过脑脊液进入中枢神经系统,这对免疫治疗策略的作用机制具有影响,例如口服耐受或治疗性免疫,其中免疫原通过口服或皮下途径施用。
Circulating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors. We reasoned that a bias (either enrichment or depletion) of CSF T cell expression of known organ-specific trafficking determinants might suggest that homing of T cells to the subarachnoid space could be governed by a CNS-specific adhesion molecule or chemokine receptor. The expression of cutaneous leukocyte antigen (CLA) and CC-chemokine receptor 4 (CCR4; associated with skin-homing) as well as the expression of integrin α4β7 and CCR9 (associated with gut-homing) was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry. CSF contained similar proportions of CD4+ memory T cells expressing CLA, CCR4, integrin α4β7 and CCR9 as paired blood samples. The results extend our previous findings that antigen-experienced CD4+ memory T cells traffic through the CSF in proportion to their abundance in the peripheral circulation. Furthermore, the ready access of skin- and gut-homing CD4+ memory T cells to the CNS compartment via CSF has implications for the mechanisms of action of immunotherapeutic strategies, such as oral tolerance or therapeutic immunization, where immunogens are administered using an oral or subcutaneous route.
DOI: 10.1084/jem.20011502
发表时间: 2002-01-07
期刊: The Journal of experimental medicine
影响因子: --
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