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

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 CD8?+ 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.

SUBMITTER: Kawabe T

PROVIDER: S-EPMC7338451 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Kawabe Takeshi T Yi Jaeu J Kawajiri Akihisa A Hilligan Kerry K Fang Difeng D Ishii Naoto N Yamane Hidehiro H Zhu Jinfang J Jankovic Dragana D Kim Kwang Soon KS Trinchieri Giorgio G Sher Alan A

Nature communications 20200706 1

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-bet< ...[more]

PMID: 32632165

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

Publications

Requirements for the differentiation of innate T-bet<sup>high</sup> memory-phenotype CD4<sup>+</sup> T lymphocytes under steady state.

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