Dynamics of Immune Responses, Institut Pasteur, Paris, France.
Immunity. 2012 Jul 27;37(1):147-57. doi: 10.1016/j.immuni.2012.05.015. Epub 2012 Jun 21.
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-γ more than 80 μm 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.
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 细胞已被证明能够将效应分子定向递送到免疫突触，这表明被感染的细胞需要单独接触以接收效应信号。相比之下，我们在这里表明，CD4(+) T 细胞稳定地接触少数被感染的细胞，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。通过使用功能读出，我们提供的证据表明，这种效应旁观者活性通过 IFN-γ 的梯度延伸超过 80μm 超出抗原呈递部位，在没有免疫突触形成的情况下促进病原体清除。因此，我们的研究结果表明，CD4(+) T 细胞可以通过与少数感染细胞接触来发挥其保护作用。
