Olive D, Cerdan C
Unit 119 of the National Institute of Health and Medical Research, Marseille, France.
Eur J Immunol. 1999 Aug;29(8):2443-53. doi: 10.1002/(SICI)1521-4141(199908)29:08<2443::AID-IMMU2443>3.0.CO;2-P.
Chemokines are key molecules in promoting leukocyte migration and, for some of them, T cell adhesion and activation. Lymphotactin, which is the unique known member of the C class of chemokines, is produced by and acts on T lymphocytes, but the requirement of co-stimulatory pathways such as CD28 for its expression is largely unknown. CD28 plays a dominant role in the amplification of T cell proliferation, survival and cytokine production. In this report, we demonstrate that human lymphotactin expression, at both the mRNA and protein levels, is optimally induced by CD3/TCR activation alone, whereas CD28 co-stimulation turns off this expression. This down-regulation is not attributable to secondary activation via CTLA-4, the alternative counter-receptor of B7 ligands. Only the CD4(+) and not the CD8(+) subset is directly affected by this negative regulation. Transcript destabilization can be ruled out as a mechanism by which CD28 down-regulates lymphotactin expression. However, such down-regulation can be partly induced by IL-2 and abrogated by blocking IL-2/IL-2 receptor interaction. This particular profile of lymphotactin expression is not in line with the prevailing dogma of up-regulation of cytokine gene expression by CD28 co-stimulation, and represents a new CD28-mediated regulatory mechanism for lymphotactin expression.
趋化因子是促进白细胞迁移的关键分子，对其中一些趋化因子而言，还能促进T细胞黏附和激活。淋巴细胞趋化因子是趋化因子C类中唯一已知的成员，由T淋巴细胞产生并作用于T淋巴细胞，但其表达对共刺激途径（如CD28）的需求在很大程度上尚不清楚。CD28在T细胞增殖、存活和细胞因子产生的放大过程中起主导作用。在本报告中，我们证明，仅通过CD3/TCR激活就能最佳地诱导人淋巴细胞趋化因子在mRNA和蛋白质水平的表达，而CD28共刺激则会关闭这种表达。这种下调并非归因于通过CTLA-4（B7配体的另一种反受体）的二次激活。只有CD4(+)亚群，而非CD8(+)亚群，直接受到这种负调控的影响。转录本不稳定可被排除为CD28下调淋巴细胞趋化因子表达的一种机制。然而，这种下调可部分由IL-2诱导，并可通过阻断IL-2/IL-2受体相互作用而消除。淋巴细胞趋化因子表达的这种特殊模式与CD28共刺激上调细胞因子基因表达的普遍观点不符，代表了一种新的CD28介导的淋巴细胞趋化因子表达调控机制。
