CD4+ T Cells Rely on a Cytokine Gradient to Control Intracellular Pathogens beyond Sites of Antigen Presentation
CD4+ T Cells Rely on a Cytokine Gradient to Control Intracellular Pathogens beyond Sites of Antigen Presentation
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DOI：
10.1016/j.immuni.2012.05.015
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发表时间：
2012-07-27
期刊：
影响因子：
32.4
通讯作者：
Bousso, Philippe
中科院分区：
文献类型：
--
作者：
Mueller, Andreas J.;Filipe-Santos, Orchidee;Bousso, Philippe
效应 T 细胞对于清除感染部位的病原体至关重要。与细胞毒性 CD8+ T 细胞一样，CD4+ 辅助 T 细胞已被证明可以向免疫突触定向传递效应分子，这表明受感染的细胞需要单独参与才能接收效应信号。相比之下，我们在此表明CD4(+) T细胞稳定地接触了少数受感染的细胞，但这些相互作用在体内触发了旁观者细胞的细胞内防御机制。通过使用功能读数，我们提供的证据表明，这种效应子旁观者活性通过 IFN-γ 梯度延伸到抗原呈递位点之外超过 80 μm，从而在没有免疫突触形成的情况下促进病原体清除。因此，我们的结果表明，CD4(+) T 细胞可以通过参与少数受感染的细胞来发挥其保护活性。
Effector T cells are critical for clearance of pathogens from sites of infection. Like cytotoxic CD8(+) T cells, CD4(+) helper T cells have been shown to deliver effector molecules directionally toward the immunological synapse, suggesting that infected cells need to be engaged individually to receive effector signals. In contrast, we show here that CD4(+) T cells stably contacted a minority of infected cells, yet these interactions triggered intracellular defense mechanisms in bystander cells in vivo. By using a functional read-out, we provide evidence that this effector bystander activity extends via a gradient of IFN-gamma more than 80 mu m beyond the site of antigen presentation, promoting pathogen clearance in the absence of immunological synapse formation. Our results thus demonstrate that CD4(+) T cells can exert their protective activity by engaging a minority of infected cells.