Memory-phenotype CD4+ T cells spontaneouslygenerated under steady state conditions exert innate Th1-like effector function

摘要

Conventional CD4⁺ T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Naïve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. Here we show that MP cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a TCR- and CD28-dependent manner. We further demonstrate that MP cells contain a T-bet^hi subpopulation that is continuously generated by environmental IL-12 and rapidly produces IFN-γ in response to IL-12 in the absence of pathogen recognition. Importantly, these cells can provide nonspecific host resistance against Toxoplasma gondii infection while enhancing the adaptive CD4⁺ T cell responses. Together, these findings reveal that MP cells are continuously generated from naïve precursors and possess a previously undescribed innate immune function by which they produce an early, Th1-like protective response against pathogens.