Brogdon Jennifer L, Leitenberg David, Bottomly Kim
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 2002 Apr 15;168(8):3825-32. doi: 10.4049/jimmunol.168.8.3825.
The potency of TCR signaling can regulate the differentiation of naive CD4(+) T cells into Th1 and Th2 subsets. In this work we demonstrate that TCR signaling by low-affinity, but not high-affinity, peptide ligands selectively induces IL-4 transcription within 48 h of priming naive CD4(+) T cells. This early IL-4 transcription is STAT6 independent and occurs before an increase in GATA-3. Furthermore, the strength of the TCR signal differentially affects the balance of NFATp and NFATc DNA binding activity, thereby regulating IL-4 transcription. Low-potency TCR signals result in high levels of nuclear NFATc and low levels of NFATp, which are permissive for IL-4 transcription. These data provide a model for how the strength of TCR signaling can influence the generation of Th1 and Th2 cells.
TCR信号的强度可调节初始CD4(+) T细胞向Th1和Th2亚群的分化。在本研究中，我们证明低亲和力而非高亲和力肽配体引发的TCR信号在初始CD4(+) T细胞启动后的48小时内选择性诱导IL-4转录。这种早期IL-4转录不依赖STAT6，且发生在GATA-3增加之前。此外，TCR信号的强度差异影响NFATp和NFATc DNA结合活性的平衡，从而调节IL-4转录。低效TCR信号导致高水平的核NFATc和低水平的NFATp，这有利于IL-4转录。这些数据为TCR信号强度如何影响Th1和Th2细胞的产生提供了一个模型。
