%0 Journal Article
%T Innate acting memory Th1 cells modulate heterologous diseases.
%A Rakebrandt N
%A Yassini N
%A Kolz A
%A Schorer M
%A Lambert K
%A Goljat E
%A Estrada Brull A
%A Rauld C
%A Balazs Z
%A Krauthammer M
%A Carballido JM
%A Peters A
%A Joller N
%J Proc Natl Acad Sci U S A
%V 121
%N 24
%D 2024 Jun 11
%M 38838013
%F 12.779
%R 10.1073/pnas.2312837121
%X 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.