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CD4+ T cells, which consist of T helper cells and T regulatory cells (Tregs) are indispensable for adaptive immunity. T helper cells are key positive regulators of both the humoral and cellular immune responses to infections, whereas Tregs attenuate immune responses and are important for tissue homeostasis. It has been known for over 30 years that CD4+ T cells are a heterogenous population that can be divided into several groups, which were largely defined in vitro according to their cytokine production profiles. First, we attempted to unravel the T cell heterogeneity in vivo at a single cell resolution. To this end, we performed single cell RNA-seq on colonic CD4+ T cells from healthy mice, as well as mice infected with pathogens that are known to skew the T cells towards particular cytokine responses. Upon infection, effector CD4+ T cells completely change and diversify their transcriptome. However, these …