Initial TCR Signal Strength Imprints GATA3 and Tbet Expression Driving T-helper Cell Fate Decisions

With the exception of the T helper 2 subset, cytokine driven pathways provide a robust mechanistic explanation for the observed outcomes of CD4 T cell differentiation. Using a quantitative model of activation, we studied the integration of TCR signal strength with cytokine signalling during Th2 differentiation. Upon the initial activation of Th-naive cells, TCR signalling was found to set early expression levels for the master regulators of differentiation Tbet and GATA3, independent of the presence of polarizing cytokines.