Ebert L M, McColl S R
Chemokine Biology Laboratory, Department of Molecular Biosciences, Adelaide University, South Australia, Australia.
J Immunol. 2001 Apr 15;166(8):4870-8. doi: 10.4049/jimmunol.166.8.4870.
Upon activation, naive T cells alter their migratory patterns, acquiring the ability to move through peripheral tissues as well as the general lymphoid circulation. Although the mechanisms responsible for these alterations are not well understood, changes in chemokine receptor expression may play a critical role. To investigate these changes, the expression patterns of two chemokine receptors, CXCR3 and CXCR4, were compared on CD4(+) T cells following activation in the MLR. By day 9 of activation, expression of the inflammatory chemokine receptor CXCR3 was up-regulated, while expression of the homeostatic chemokine receptor CXCR4 was down-regulated. Alterations in receptor expression occurred almost exclusively on a subpopulation of T cells that expressed higher levels of CD4. These CD4(high) T cells demonstrated many characteristics of activated T cells and had undergone division in the MLR. By day 9 of culture, the majority of CXCR3(+) and CXCR4(-) cells had divided and had acquired an activated/memory phenotype (CD45RA(-) CD45RO(+) CD69(+) CD25(+)). The levels of transcripts for both CXCR3 and CXCR4 were increased upon allo-activation. The discrepancy between levels of CXCR4 mRNA and surface protein was not due to sequestration of the receptor in intracellular compartments, as CXCR4 was not detectable intracellularly. However, intracellular CXCR3 was readily detectable. Finally, cells from allogeneic cultures demonstrated enhanced migration toward IFN-inducible T cell alpha chemoattractant and reduced migration toward stromal cell-derived factor-1 compared with syngeneic controls, thus suggesting that the observed switch in receptor expression may at least partly contribute to the differential patterns of migration displayed by naive and memory T cells.
在被激活后，初始T细胞会改变其迁移模式，获得在周围组织以及整个淋巴循环中移动的能力。尽管导致这些改变的机制尚未完全明确，但趋化因子受体表达的变化可能起着关键作用。为了研究这些变化，在混合淋巴细胞反应（MLR）激活后，比较了两种趋化因子受体CXCR3和CXCR4在CD4(+) T细胞上的表达模式。到激活第9天时，炎性趋化因子受体CXCR3的表达上调，而稳态趋化因子受体CXCR4的表达下调。受体表达的改变几乎只发生在表达较高水平CD4的T细胞亚群上。这些CD4(高) T细胞表现出许多活化T细胞的特征，并在MLR中发生了分裂。到培养第9天时,大多数CXCR3(+)和CXCR4(-)细胞已经分裂并获得了活化/记忆表型(CD45RA(-) CD45RO(+) CD69(+) CD25(+))。同种异体激活后，CXCR3和CXCR4的转录本水平均升高。CXCR4 mRNA水平与表面蛋白水平之间的差异并非由于受体被隔离在细胞内区室中,因为细胞内未检测到CXCR4。然而，细胞内CXCR3很容易被检测到。最后，与同基因对照相比，来自异基因培养物的细胞对干扰素诱导的T细胞α趋化因子的迁移增强，而对基质细胞衍生因子-1的迁移减少，因此表明观察到的受体表达转换可能至少部分有助于初始T细胞和记忆T细胞所表现出的不同迁移模式。
