Lymphocyte Cell Biology Unit, Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
PLoS One. 2011 May 10;6(5):e18553. doi: 10.1371/journal.pone.0018553.
The role of T cells in innate immunity is not well defined. In this report, we show that a subset of human peripheral blood CD4(+) T cells responds to IL-12 plus IL-18, but not to IL-12 or IL-18 alone, by producing IFN-γ in the absence of any antigenic stimulation or cell proliferation. Intracellular staining reveals a small percentage of resting CD4(+) T cells (0.5 to 1.5%) capable of producing IFN-γ in response to IL-12 plus IL-18. Interestingly, both naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) populations were responsive to IL-12 plus IL-18 stimulation in producing IFN-γ. The expression of IFN-γinduced by IL-12 and IL-18 is sensitive to rapamycin and SB203580, indicating the possible involvement of mTOR and p38 MAP kinase, respectively, in this synergistic pathway. While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization. We have also shown that NFκB family member, cRel, but not GADD45β and GADD45γ, plays an important role in IL-12 plus IL-18-induced IFN-γ transcription. Thus, the present study suggests that naïve CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production.
T 细胞在天然免疫中的作用尚未完全明确。在本报告中，我们发现，人类外周血 CD4(+)T 细胞的一个亚群在没有任何抗原刺激或细胞增殖的情况下，对 IL-12 加 IL-18 的反应是产生 IFN-γ。细胞内染色显示，一小部分静止的 CD4(+)T 细胞（0.5 至 1.5%）能够对 IL-12 加 IL-18 产生 IFN-γ反应。有趣的是，幼稚（CD45RA(+)）和记忆（CD45RO(+)）CD4(+)群体对 IL-12 加 IL-18 的刺激都能产生 IFN-γ。IL-12 和 IL-18 诱导的 IFN-γ表达对 rapamycin 和 SB203580 敏感，表明 mTOR 和 p38MAP 激酶分别参与了这条协同途径。虽然 p38MAP 激酶参与转录，而 mTOR 则参与信息稳定。我们还表明，NFκB 家族成员 cRel 而非 GADD45β 和 GADD45γ 在 IL-12 加 IL-18 诱导的 IFN-γ转录中发挥重要作用。因此，本研究表明，幼稚 CD4(+)T 细胞可能通过细胞因子诱导的抗原非依赖性细胞因子产生参与天然免疫或放大适应性免疫反应。
