Innate acting memory Th1 cells modulate heterologous diseases

• 成果类型: Article
• 署名作者: Rakebrandt, Nikolas; Yassini, Nima; Kolz, Anna; Schorer, Michelle; Lambert, Katharina; Goljat, Eva; Brull, Anna Estrada; Rauld, Celine; Balazs, Zsolt; Krauthammer, Michael; Carballido, Jose M.; Peters, Anneli; Joller, Nicole
• 署名单位: University of Zurich; University of Zurich; University of Munich; Novartis; University of Munich
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10678
• DOI: 10.1073/pnas.2312837121
• 发表日期: 2024-06-11
• 关键词: human immune-system; cd8(+) t-cells; lymphocyte egress; gamma production; transgenic mice; severe covid-19; activation; responses; nkg2d; expression

摘要

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-gamma 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-gamma 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.