The study found that CD4+ T cells exist on a continuum of effectorness, from naive to effector memory, which influences their response to cytokines. Memory T cells, unlike naive T cells, can't become Th2 cells and actually develop Th17-like characteristics when exposed to iTreg-polarizing conditions.

None identified

This is a strong study with a robust experimental design and comprehensive data analysis. The study provides new insights into the heterogeneity of T cell responses and identifies an effectorness gradient that shapes the response of T cells to cytokines. The study also reveals that memory T cells are unable to differentiate into the Th2 phenotype and acquire a Th17-like phenotype in response to iTreg polarization. These findings have important implications for our understanding of T cell biology and could lead to the development of new treatments for immune-mediated diseases. However, the study is limited by its focus on in vitro experiments and by the use of a single stimulation time point for bulk RNA-seq and proteomics.