1. Academic Validation
  2. Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

  • Signal Transduct Target Ther. 2024 Feb 28;9(1):43. doi: 10.1038/s41392-024-01752-0.
Jun Zhou # 1 2 Jiaqi Liu # 3 Bingjing Wang 3 Nan Li 2 Juan Liu 2 Yanmei Han 4 Xuetao Cao 5 6 7 8
Affiliations

Affiliations

  • 1 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 2 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai, 200433, China.
  • 3 Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
  • 4 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai, 200433, China. hanyanmei@immunol.org.
  • 5 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China. caoxt@immunol.org.
  • 6 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai, 200433, China. caoxt@immunol.org.
  • 7 Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. caoxt@immunol.org.
  • 8 Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, 300071, China. caoxt@immunol.org.
  • # Contributed equally.
Abstract

Memory CD8+ T cell generation is crucial for pathogen elimination and effective vaccination against Infection. The cellular and molecular circuitry that underlies the generation of memory CD8+ T cells remains elusive. Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense. Here we report that eosinophils are required for the generation of memory CD8+ T cells by inhibiting CD8+ T cell Apoptosis. Eosinophil-deficient mice display significantly impaired memory CD8+ T cell response and weakened resistance against Listeria monocytogenes (L.m.) Infection. Mechanistically, eosinophils secrete interleukin-4 (IL-4) to inhibit JNK/Caspase-3 dependent Apoptosis of CD8+ T cells upon L.m. Infection in vitro. Furthermore, active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+ T cell Apoptosis during early stage of L.m. Infection in vivo. Adoptive transfer of wild-type (WT) eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+ T cell memory responses. Together, our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+ T cell memory and enhances immune defense against L.m. Infection. Our study reveals a new Adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

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