Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state
Takeshi Kawabe, Jaeu Yi, Akihisa Kawajiri, Kerry L. Hilligan, Difeng Fang, Naoto Ishii, Hidehiro Yamane, Jinfang Zhu, Dragana Janković, Kwang Soon Kim, Giorgio Trinchieri, Alan Sher
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-bet high , T-bet low , and T-bet − subsets, with innate, Th1-like effector activity exclusively associated with T-bet high 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-bet high MP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels.