Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
Department of Quantitative Biomedicine, University of Zurich, 8057 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2312837121. doi: 10.1073/pnas.2312837121. Epub 2024 Jun 5.
Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (T) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory T cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory T cells is protective in subsequent heterologous challenge with the bacterial pathogen . In contrast, antigen-independent reactivation of CD4 memory T cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges.
通过免疫记忆，感染对宿主产生持久的影响。虽然记忆细胞能够在再次遇到相同病原体时加速和增强反应，但它们对与无关疾病的易感性的影响尚不清楚。我们鉴定出了一组称为先天作用记忆 T（T）细胞的记忆辅助性 T 细胞（Th1）亚群，它们源自病毒感染，并在体内异体挑战时以先天的动力学产生 IFN-γ。记忆 T 细胞的激活是响应 IL-12 与 IL-18 或 IL-33 的组合而诱导的，而与 TCR 无关。记忆 T 细胞的快速 IFN-γ产生在随后的细菌病原体异体挑战中具有保护作用。相比之下，在多发性硬化症的自身免疫模型中，抗原非依赖性 CD4 记忆 T 细胞的重新激活加速了疾病的发作。我们的发现表明，记忆 Th1 细胞可以获得额外的 TCR 非依赖性功能，以快速产生类似先天的反应，从而调节对异体挑战的易感性。
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