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Memory programming in CD8+ T-cell differentiation is intrinsic and is not determined by CD4 help

Author

Listed:
  • Juhyun Kim

    (Seoul National University College of Medicine)

  • Su Jeong Ryu

    (Seoul National University College of Medicine)

  • Keunhee Oh

    (Seoul National University College of Medicine)

  • Ji-Min Ju

    (Seoul National University College of Medicine)

  • Ji Yeong Jeon

    (Seoul National University College of Medicine)

  • Giri Nam

    (Seoul National University College of Medicine)

  • Dong-Sup Lee

    (Seoul National University College of Medicine)

  • Hang-Rae Kim

    (Seoul National University College of Medicine)

  • Joo Young Kim

    (Ewha Womans University)

  • Jun Chang

    (Ewha Womans University)

  • Thomas Sproule

    (The Jackson Laboratory)

  • Kyungho Choi

    (Seoul National University College of Medicine)

  • Derry Roopenian

    (The Jackson Laboratory)

  • Eun Young Choi

    (Seoul National University College of Medicine)

Abstract

CD8+ T cells activated without CD4+ T-cell help are impaired in memory expansion. To understand the underlying cellular mechanism, here we track the dynamics of helper-deficient CD8+ T-cell response to a minor histocompatibility antigen by phenotypic and in vivo imaging analyses. Helper-deficient CD8+ T cells show reduced burst expansion, rapid peripheral egress, delayed antigen clearance and continuous activation, and are eventually exhausted. Contrary to the general consensus that CD4 help encodes memory programmes in CD8+ T cells and helper-deficient CD8+ T cells are abortive, these cells can differentiate into effectors and memory precursors. Importantly, accelerating antigen clearance or simply increasing the burst effector size enables generation of memory cells by CD8+ T cells, regardless of CD4 help. These results suggest that the memory programme is CD8+ T-cell-intrinsic, and provide insight into the role of CD4 help in CD8+ T-cell responses.

Suggested Citation

  • Juhyun Kim & Su Jeong Ryu & Keunhee Oh & Ji-Min Ju & Ji Yeong Jeon & Giri Nam & Dong-Sup Lee & Hang-Rae Kim & Joo Young Kim & Jun Chang & Thomas Sproule & Kyungho Choi & Derry Roopenian & Eun Young Ch, 2015. "Memory programming in CD8+ T-cell differentiation is intrinsic and is not determined by CD4 help," Nature Communications, Nature, vol. 6(1), pages 1-17, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8994
    DOI: 10.1038/ncomms8994
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    1. Youmei Xiao & Zhuoying He & Wanqiong Li & Danhong Chen & Xiaoshuang Niu & Xin Yang & Wenxuan Zeng & Mengfan Wang & Yuzhen Qian & Ye Su & Feiyu Luo & Guanyu Chen & Juan Liu & Xinghua Sui & Xiuman Zhou , 2025. "A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

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