Gagnon Julien, Ramanathan Sheela, Leblanc Chantal, Cloutier Alexandre, McDonald Patrick P, Ilangumaran Subburaj
Immunology Division, Department of Pediatrics, University of Sherbrooke, Québec, Canada.
J Immunol. 2008 Jun 15;180(12):7958-68. doi: 10.4049/jimmunol.180.12.7958.
Recent reports have shown that IL-21, in synergy with IL-15, stimulates proliferation of CD8(+) T lymphocytes in the absence of signaling via the TCR. In this study, we show that IL-6, which induces phosphorylation of STAT3 similarly to IL-21, also can stimulate proliferation of CD8(+) T cells in synergy with IL-7 or IL-15. IL-6 displays a stronger synergy with IL-7 than with IL-15 to stimulate naive CD8(+) T cells. Concomitant stimulation by IL-6 or IL-21 augments phosphorylation and DNA-binding activity of STAT5 induced by IL-7 or IL-15. Like IL-21, IL-6 reduces the TCR signaling threshold required to stimulate CD8(+) T cells. Prior culture of P14 TCR transgenic CD8 T cells with IL-6 or IL-21 in the presence of IL-7 or IL-15 augments their proliferation and cytolytic activity upon subsequent stimulation by Ag. Furthermore, cytokine stimulation induces quantitatively and qualitatively distinct phenotypic changes on CD8(+) T cells compared with those induced by TCR signaling. We propose that the ability of IL-6 to induce TCR-independent activation of CD8(+) T cells in synergy with IL-7 or IL-15 may play an important role in the transition from innate to adaptive immunity.
最近的报告显示，白细胞介素-21（IL-21）与白细胞介素-15（IL-15）协同作用，在缺乏通过T细胞受体（TCR）信号传导的情况下刺激CD8(+) T淋巴细胞增殖。在本研究中，我们发现，与IL-21类似可诱导信号转导和转录激活因子3（STAT3）磷酸化的IL-6，也能与IL-7或IL-15协同刺激CD8(+) T细胞增殖。IL-6与IL-7协同刺激初始CD8(+) T细胞时，比与IL-15表现出更强的协同作用。IL-6或IL-21的联合刺激增强了由IL-7或IL-15诱导的STAT5磷酸化和DNA结合活性。与IL-21一样，IL-6降低了刺激CD8(+) T细胞所需的TCR信号阈值。在IL-7或IL-15存在的情况下，用IL-6或IL-21对P14 TCR转基因CD8 T细胞进行预培养，可增强其在随后受到抗原刺激时的增殖和细胞溶解活性。此外，与TCR信号传导诱导的变化相比，细胞因子刺激在CD8(+) T细胞上诱导出数量和质量上均不同的表型变化。我们提出，IL-6与IL-7或IL-15协同诱导CD8(+) T细胞非TCR依赖性激活的能力，可能在从固有免疫向适应性免疫的转变中起重要作用。
