Chemokine receptors and T cell chemotaxis.
Chemokine receptors and T cell chemotaxis.
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DOI：
10.1084/jem.184.3.799
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发表时间：
1996-09-01
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T细胞的迁移是一个高度调控的过程，将细胞的功能亚群分配到适当的组织或微环境中。黏附分子在这一过程中的作用得到了很好的认识(1，2)然而，另一类分子，趋化细胞因子(趋化因子)及其受体，现在正受到相当大的关注，因为它们不仅在白细胞迁移中发挥基础作用，而且在造血、T细胞激活和白细胞脱颗粒中也发挥重要作用(3)。此外，最近的一系列论文表明，趋化因子受体在HIV-1进入细胞的过程中扮演辅助因子的角色(参考文献4，5)。这期杂志上的两篇论文大大加深了我们对趋化因子及其受体在T细胞运输中的作用的理解。趋化因子有两个主要家族，CXC和CC，根据NH2末端附近一对半胱氨酸残基之间是否存在氨基酸而被称为CXC和CC。最早被发现的趋化因子成员之一是1985年的IP-10(6)，现在已知存在40个或更多。最早的趋化因子受体是几年前发现的(7，8)，发现有7种跨膜受体(7TMP，…)，它们通过G蛋白相互作用(3，9，10)传递信号。7TMR对经典的趋化物质，如fmlp和C5a(11)也起作用，也对原始物种的趋化作用，如Dictyostelials(12)。表1列出了迄今为止已定义的人类趋化因子受体。其中许多受体的确切表达尚不清楚，因为尚不能获得特定的单抗。对于T细胞，pCI：K或Northern blotting表明已知的五种CC趋化因子受体，定义为CCR1至CCR5(1996年戈登趋化细胞因子研究会议通过了CC和CXC趋化因子受体的新命名)。见表1)，表达在T细胞亚群上。准确地描述哪些亚群是一个深入研究的领域，因为趋化因子受体的表达可以解释各种细胞类型的定位或迁移，如TH1或TH2T细胞，或组织归巢亚群。它还可以确定哪些T细胞感染了不同的HIV-1毒株。一个令人惊讶的发现是，在T谱系中，许多已知的趋化因子受体仅限于激活或记忆(CD45RO+)型细胞。CD45RO+T细胞的确切性质尚不清楚(13)，但它们在体外黏附特性和体内迁移模式方面确实显示出与CD45RA+T细胞的重大差异(13，14)。MCP-1受体(CCP、.2)是
T he migration of T cells is a highly regulated process, serving to distribute functional subsets of cells to the appropriate tissue or microenvironment. The role of adhesion molecules in this process is well appreciated (1, 2) however an additional class of molecules, the chemoattractant cytokines (chemokines) and their receptors, are now receiving considerable attention, because of their fundamental role not only in leukocyte migration, but also in hematopoiesis, T cell activation, and leukocyte degranulation (3). In addition, a recent flurry of papers has demonstrated that chemokine receptors act as cofactors for HIV-1 entry into cells (reviewed in references 4, 5). Two papers in the current issue of this journal add significantly to our understanding of the role of chemokines and their receptors in T cell traffic.There are two major families of chemokines, termed CXC and CC according to the presence or absence of an amino acid between a pair of cysteine residues near the NH 2 terminus. One of the first members of the chemokines to be identified was IP-10, in 1985 (6), and now 40 or more are known to exist. The first receptors for chemokines were identified several years ago (7, 8), and were found to be seven transmembrane spanning receptors (7TMP,.), that signal through G protein interactions (3, 9, 10). 7TMR also function for the classical chemoattractants, such as fmlp and C5a (11), and also for the chemotaxis of primitive species such as Dictyostelium (12). The human chemokine receptors that have been defined to date are listed in Table 1. The precise expression of many of these receptors is not yet known, because specific mAbs are not available. For T cells, PCI: k or northern blotting indicates that the five known receptors for CC chemokines, defined as CCR1 to CCR5 (A new nomenclature for CC and CXC chemokine receptors was adopted at the 1996 Gordon Research conference on chemotactic cytokines. See Table 1.), are expressed on subsets of T cells. Delineating exactly which subsets is an area of intense study, because chemokine receptor expression may explain the localization or migration of various cell types, such as TH1 or TH2 T cells, or tissue homing subsets. It may also determine which T cells are infected with different strains of HIV-1. A surprising finding is that, within the T lineage, many of the known chemokine receptors are restricted to activated or memory (CD45RO+) type cells. The exact nature of CD45RO+ T cells is still unclear (13), however they do show major differences from CD45RA+ T ceils with respect to adhesion properties in vitro, and migration patterns in vivo (13, 14). The MCP-1 receptor (CCP,. 2) is