Abbal C, Jourdan P, Hori T, Bousquet J, Yssel H, Pène J
INSERM U454, Hôpital Arnaud de Villeneuve, 375 Avenue Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France.
Int Immunol. 1999 Sep;11(9):1451-62. doi: 10.1093/intimm/11.9.1451.
The selective migration of functional T(h) lymphocyte subsets with different cytokine production profiles into inflamed tissue is likely to depend on the state of activation of the cells, as well as on the differential expression of various adhesion molecules and chemokine receptors. In this study, we have analyzed the effect of allergen-specific activation on the expression of the chemokine receptor CXCR4 on T lymphocytes. We show that stimulation of peripheral blood mononuclear cells from atopic patients with the allergen Der p results in down-regulation of CXCR4 surface expression on Der p-activated CD25(+)CD45RO(+) antigen-specific memory cells which was caused by a decrease in CXCR4 gene transcription and did not seem to be mediated by endogenous cytokines, such as IFN-gamma. In contrast, however, CXCR4 surface expression was enhanced on naive CD25(-)CD45RO(-) and resting CD25(-)CD45RO(+) memory T cells, as a result of the presence of endogenous IL-4, most likely produced by Der p-activated memory T cells. Antigen-specific CD25(+)CD45RO(+) T lymphocytes, purified 7 days after stimulation with Der p, had a strongly reduced capacity to migrate in response to stimulation with stromal cell-derived factor (SDF)-1, the ligand for CXCR4. Together, these results suggest that differential expression of CXCR4 on activated and resting T cells is due to the counteracting effects of TCR-mediated down-regulation and IL-4-mediated up-regulation of this chemokine receptor respectively, and furthermore indicate that antigen-activated memory T cells are unlikely to migrate into inflamed tissue in response to SDF-1.
具有不同细胞因子产生谱的功能性辅助性T淋巴细胞亚群向炎症组织的选择性迁移可能取决于细胞的激活状态，以及各种黏附分子和趋化因子受体的差异表达。在本研究中，我们分析了变应原特异性激活对T淋巴细胞趋化因子受体CXCR4表达的影响。我们发现，用变应原Der p刺激特应性患者的外周血单个核细胞，会导致Der p激活的CD25(+)CD45RO(+)抗原特异性记忆细胞表面CXCR4表达下调，这是由CXCR4基因转录减少引起的，且似乎不是由内源性细胞因子如干扰素-γ介导的。然而，相比之下，由于内源性IL-4（很可能由Der p激活的记忆T细胞产生）的存在，幼稚的CD25(-)CD45RO(-)和静息的CD25(-)CD45RO(+)记忆T细胞表面CXCR4表达增强。用Der p刺激7天后纯化的抗原特异性CD25(+)CD45RO(+)T淋巴细胞，对基质细胞衍生因子（SDF）-1（CXCR4的配体）刺激的迁移反应能力大幅降低。总之，这些结果表明，激活的和静息的T细胞上CXCR4的差异表达分别是由于该趋化因子受体的TCR介导的下调和IL-4介导的上调的抵消作用，并且还表明抗原激活的记忆T细胞不太可能响应SDF-1迁移到炎症组织中。
