Evidence that rapamycin inhibits interleukin-12-induced proliferation of activated T lymphocytes.
Evidence that rapamycin inhibits interleukin-12-induced proliferation of activated T lymphocytes.
复制标题
DOI：
10.1097/00007890-199411000-00006
复制
发表时间：
1994-11
期刊：
影响因子：
6.2
通讯作者：
Monica M. Bertagnolli;Lin Yang;Steven H. Herrmann;R. Kirkman
中科院分区：
文献类型：
--
作者：
Monica M. Bertagnolli;Lin Yang;Steven H. Herrmann;R. Kirkman
白介素12是一种异源二聚体细胞因子，参与调节自然杀伤细胞和T淋巴细胞反应。在以前的研究中，我们发现IL-12只有在与凝集素、同种异体抗原或抗CD3抗体共同刺激时才能诱导T细胞增殖。以这种方式产生的IL-2介导的长期T细胞系的增殖通常对免疫抑制剂环孢菌素不敏感，但对雷帕霉素敏感。在这项研究中，我们研究了环孢素和雷帕霉素对IL-12应答的T细胞的影响。对于长期培养的T细胞系，在植物血凝素、同种异体抗原或固相抗CD3抗体刺激下，雷帕霉素将IL-12诱导的增殖抑制到背景水平。环孢素对IL-12诱导的T细胞增殖的抑制作用最小。新鲜分离的CD3+细胞对IL-12没有反应而增殖，在IL-12中培养也没有导致IL-2受体的上调。这些数据表明，IL-12是激活的T淋巴细胞的重要生长调节剂，其作用可能与晚期细胞激活事件有关。
Interleukin 12 is a heterodimeric cytokine involved in the regulation of natural killer cell and T lymphocyte responses. In previous studies, we found that IL-12 induces proliferation of T cells only after co-stimulation with lectin, alloantigen, or anti-CD3 antibody. The IL-2-mediated proliferation of long-term T cell lines generated in this fashion is typically insensitive to the immunosuppressive agent, cyclosporine but sensitive to rapamycin. In this study, we examined the effect of cyclosporine and rapamycin on T cells responsive to IL-12. For long-term cultured T cell lines stimulated with phytohemagglutinin, alloantigen, or solid-phase anti-CD3 antibody, rapamycin blocked IL-12-induced proliferation to background levels. Culture in cyclosporine produced minimal inhibition of IL-12-induced T cell proliferation. Freshly isolated CD3+ cells did not proliferate in response to IL-12, nor did culture of these cells in IL-12 lead to upregulation of IL-2 receptor. These data suggest that the effect of IL-12, an important growth regulator for activated T lymphocytes, may involve late cellular activation events.