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Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state

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  • Takeshi Kawabe

    (Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
    Tohoku University Graduate School of Medicine)

  • Jaeu Yi

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology)

  • Akihisa Kawajiri

    (Tohoku University Graduate School of Medicine)

  • Kerry Hilligan

    (Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
    Malaghan Institute of Medical Research)

  • Difeng Fang

    (Laboratory of Immune System Biology, NIAID, NIH)

  • Naoto Ishii

    (Tohoku University Graduate School of Medicine)

  • Hidehiro Yamane

    (Vaccine Research Center, NIAID, NIH)

  • Jinfang Zhu

    (Laboratory of Immune System Biology, NIAID, NIH)

  • Dragana Jankovic

    (Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH))

  • Kwang Soon Kim

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology)

  • Giorgio Trinchieri

    (Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH)

  • Alan Sher

    (Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH))

Abstract

CD4+ T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether MP CD4+ T cells are functionally heterogeneous and, if so, what signals specify the differentiation of MP cell subpopulations under homeostatic conditions is still unclear. Here we characterize MP lymphocytes as consisting of T-bethigh, T-betlow, and T-bet− subsets, with innate, Th1-like effector activity exclusively associated with T-bethigh cells. We further show that the latter population depends on IL-12 produced by CD8α+ type 1 dendritic cells (DC1) for its differentiation. Finally, our data demonstrate that this tonic IL-12 production requires TLR-MyD88 signaling independent of foreign agonists, and is further enhanced by CD40-CD40L interactions between DC1 and CD4+ T lymphocytes. We propose that optimal differentiation of T-bethigh MP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels.

Suggested Citation

  • Takeshi Kawabe & Jaeu Yi & Akihisa Kawajiri & Kerry Hilligan & Difeng Fang & Naoto Ishii & Hidehiro Yamane & Jinfang Zhu & Dragana Jankovic & Kwang Soon Kim & Giorgio Trinchieri & Alan Sher, 2020. "Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17136-1
    DOI: 10.1038/s41467-020-17136-1
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