IL-12 derived from CD8α+ dendritic cells drives the differentiation of innate-like T-bethigh memory-phenotype CD4+ T lymphocytes in steady state

Abstract

Abstract CD4+ T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments in steady state. We recently showed that MP cells exert innate-like effector function in host defense. However, it remained to be defined whether MP cell population comprises multiple subsets, and if so, what factors determine their selective differentiation under homeostatic conditions. 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 steady-state differentiation of T-bethigh MP cells is promoted by IL-12-producing CD8α+ dendritic cells (DC1). Finally, we present evidence arguing that this tonic IL-12 production requires TLR-MyD88 signaling triggered independently of foreign agonists and is further enhanced by CD40-CD40L interactions with self-dependent MP CD4+ T lymphocytes. Thus, optimal differentiation of T-bethigh MP lymphocytes in steady state requires IL-12 tonically produced by DC1 in an MyD88 and CD40 signaling-dependent fashion. This work was in part supported by the Intramural Research Program of the NIAID and NCI, NIH.