Effects of intracellular communication between T helper cells on Th2 differantiation

Abstract

Cytokines provide a main regulatory mechanism of immune responses, which allows for intercellular communication and enables cells to make collective decisions. Existing evidence for stochastiticity in expression of cytokines and their receptors raises the question: how does cytokine communication performs reliably in the face of noise? We study the effect of heterogeneity in IL4R expression level during Th2 differentiation as a model system. Naïve CD4 T cells were separated into different groups according to their IL4R expression levels and the different groups were cultured separately, under different IL4 concentrations driving their differentiation. Expression levels of Th2 markers, IL4 and GATA3, were measured at the single cell level. Our results reveal differences in the differentiation abilities of the different groups - higher initial receptor levels facilitate faster Th2 differentiation, at lower levels of IL4 as an input. Interestingly, we found that these differences in the differentiation abilities vanish when cells with high and low initial IL4R levels are co-cultured. These results suggest that intercellular interactions can decrease the potential heterogeneity in the population that results from noise in gene expression. These experiments provide an opportunity to evaluate the importance and roles played by intercellular communication in Th cell differentiation, and to assess the effects of stochasticity in protein levels on the differentiation process.