AbstractNaïve T cells are generally considered to be a homogeneous population, but for their unique T cell receptors (TCRs). Naïve T cells are activated within a specific cytokine milieu upon interaction with antigen-presenting cells through cognate TCR::MHC-peptide interaction and co-stimulation. Here we demonstrate that naïve T cells are transcriptionally heterogeneous, and that the relative proportions of transcriptionally distinct naïve T cell subpopulations are modified by immune responses, such as during helminth infection. Not only are cognate naïve T cells activated during an immune response, but the cytokine produced - such as IL-4 during helminth infection - changes the transcriptome of bystander naïve T cells. Such changes in gene expression and population level heterogeneity in bystander naïve T cells result in altered responses to a concurrent immune challenge, for instance, hypo-responsiveness to vaccination. Thus, naïve T cell activation is not the result of a singular temporal event, but is characterized by hysteresis. Our studies suggest that antigen-agnostic, cytokine-dependent naïve T cell conditioning and resulting hysteresis is a mechanism that integrates input signals from concurrent infections for the regulation of the overall magnitude of the immune response.
Two strains of probiotic Lactobacillus enhance immune response and promote naive T cell polarization to Th1
