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

Takeshi Kawabe (), Jaeu Yi, Akihisa Kawajiri, Kerry Hilligan, Difeng Fang, Naoto Ishii, Hidehiro Yamane, Jinfang Zhu, Dragana Jankovic, Kwang Soon Kim, Giorgio Trinchieri and Alan Sher ()
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Takeshi Kawabe: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
Jaeu Yi: Academy of Immunology and Microbiology, Institute for Basic Science
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)
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
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)

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17136-1

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