IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway
IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway
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DOI：
10.4049/jimmunol.0801792
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发表时间：
2009-06-01
影响因子：
4.4
通讯作者：
Cerf-Bensussan, Nadine
中科院分区：
文献类型：
--
作者：
Ahmed, Melika Ben;Hmida, Nadia Belhadj;Cerf-Bensussan, Nadine
IL-15在几种人类疾病中驱动慢性炎症。我们最近发现IL-15通过阻断Smad 3信号通路抑制TGF-β的免疫抑制作用。TGF-β和CD 4（+）调节性T细胞之间相互作用的数据使我们研究了IL-15对人类调节性T细胞从头产生和功能的影响。我们的数据表明，IL-15不抵消，而是促进TGF-β对调节性T细胞（Treg）从头生成的影响。因此，在存在TGF-β的情况下，IL-15增强了由抗CD 3和抗CD 28 Ab刺激的CD 4（+）CD 25（-）T细胞对调节功能的获得。相反，IL-15通过作用于效应CD 4和CD 8 T细胞而损害TcB的功能。因此，在IL-15的存在下，外周CD 4和CD 8 T细胞的增殖和IFN-γ的产生不能被Tclase有效地抑制。IL-15诱导的效应T细胞对TGFAP的抗性是由PI 3 K信号通路的激活引起的，但不涉及拯救效应T细胞免于凋亡。总之，这些数据表明EL-15在调节性T细胞功能控制中的作用不明确。这种双重作用可能有助于对病原体产生快速但短暂的促炎性免疫应答，但在与长期IL-15过表达相关的情况下可能变得有害。免疫学杂志，2009，182：6763-6770.
IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted from activation of the PI3K signaling pathway but did not involve the rescue of effector T cells from apoptosis. Altogether, these data point to the ambiguous role of EL-15 in the control of Treg functions. This dual role may be instrumental to mount rapid but transient proinflammatory immune responses against pathogens but may become deleterious in situations associated with protracted IL-15 over-expression. The Journal of Immunology, 2009, 182: 6763-6770.