Nikolas Rakebrandt, Nima Yassini, Anna Kolz, Michelle Schorer, Katharina Lambert, Eva Goljat, Anna Estrada Brull, Celine Rauld, Zsolt Balazs, Michael Krauthammer, José M Carballido, Anneli Peters, Nicole Joller
Proceedings of the National Academy of Sciences of the United States of America 2024 Jun 11Through 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 (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA 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 TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA 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.
Nikolas Rakebrandt, Nima Yassini, Anna Kolz, Michelle Schorer, Katharina Lambert, Eva Goljat, Anna Estrada Brull, Celine Rauld, Zsolt Balazs, Michael Krauthammer, José M Carballido, Anneli Peters, Nicole Joller. Innate acting memory Th1 cells modulate heterologous diseases. Proceedings of the National Academy of Sciences of the United States of America. 2024 Jun 11;121(24):e2312837121
PMID: 38838013
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