Innate acting memory Th1 cells modulate heterologous diseases.

Rakebrandt, Nikolas; Yassini, Nima; Kolz, Anna; Schorer, Michelle; Lambert, Katharina; Goljat, Eva; Estrada Brull, Anna; Rauld, Celine et al. · Proc Natl Acad Sci U S A · 2024

basic_science · Level V

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Abstract

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<sub>IA</sub>) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory T<sub>IA</sub> 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<sub>IA</sub> cells is protective in subsequent heterologous challenge with the bacterial pathogen <i>Legionella pneumophila</i>. In contrast, antigen-independent reactivation of CD4<sup>+</sup> memory T<sub>IA</sub> 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.

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