Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells.
Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells.
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DOI：
10.1182/blood-2006-04-018101
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发表时间：
2007-01
期刊：
影响因子：
20.3
通讯作者：
T. Yasuda;T. Kuwabara;H. Nakano;K. Aritomi;T. Onodera;M. Lipp;Y. Takahama;T. Kakiuchi
中科院分区：
文献类型：
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作者：
T. Yasuda;T. Kuwabara;H. Nakano;K. Aritomi;T. Onodera;M. Lipp;Y. Takahama;T. Kakiuchi
次级淋巴器官（SLO）为T细胞应答的启动和调节提供了一个小生境，但其机制尚不清楚。我们研究了在SLO中组成型表达的趋化因子CCL 19和CCL 21对CD 4 + T细胞的活化诱导细胞死亡（AICD）的影响。当用OVA/CFA致敏缺乏CCL 19/CCL 21表达的淋巴结T细胞（plt）突变小鼠时，与野生型（WT）小鼠的应答相比，引流淋巴结中OVA应答性CD 4 + T细胞的扩增和体外回忆应答均延长。在克隆扩增期，plt/plt和WT小鼠中OVA应答性CD 4 + T细胞的凋亡细胞频率同样较低。然而，在克隆收缩期，频率从未增加plt/plt小鼠，而在WT小鼠中，它不断增加到免疫后18天的峰值。在用抗-CD 3加抗-CD 28体外刺激CD 4 + T细胞的过程中，CCL 19/CCL 21的存在显著增强了再刺激的T细胞的体外AICD诱导，部分通过增强Fas配体的表达。我们的研究结果表明，由基质细胞和抗原呈递细胞产生的CCL 19/CCL 21通过促进AICD来调节SLO中的CD 4 + T细胞免疫应答。
Secondary lymphoid organs (SLOs) provide a niche for the initiation and regulation of T-cell responses, but the mechanisms have been poorly understood. We investigated the influence of chemokines CCL19 and CCL21 constitutively expressed in SLOs on activation-induced cell death (AICD) of CD4+ T cells. When paucity of lymph node T cells (plt) mutant mice lacking expression of CCL19/CCL21 were primed with OVA/CFA, both expansion of OVA-responding CD4+ T cells in the draining lymph nodes and an in vitro recall response were prolonged as compared with responses in wild-type (WT) mice. The apoptotic cell frequency among OVA-responding CD4+ T cells was similarly low in plt/plt and WT mice during the clonal expansion phase. However, during the clonal contraction phase, the frequency never increased in plt/plt mice, whereas in WT mice it continuously increased to a peak 18 days after immunization. The presence of CCL19/CCL21 during the in vitro stimulation of CD4+ T cells with anti-CD3 plus anti-CD28 significantly enhanced in vitro AICD induction of the restimulated T cells, partially through enhancing expression of Fas ligand. Our results suggest that CCL19/CCL21 produced by stromal cells and antigen-presenting cells regulate CD4+ T-cell immune responses in SLOs by promoting AICD.