{Reference Type}: Journal Article
{Title}: Innate acting memory Th1 cells modulate heterologous diseases.
{Author}: Rakebrandt N;Yassini N;Kolz A;Schorer M;Lambert K;Goljat E;Estrada Brull A;Rauld C;Balazs Z;Krauthammer M;Carballido JM;Peters A;Joller N;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 121
{Issue}: 24
{Year}: 2024 Jun 11
{Factor}: 12.779
{DOI}: 10.1073/pnas.2312837121
{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 (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.