CD4+ T Cell Differentiation is Determined During an Initial Priming Phase and Occurs Independently of Effects due to Division or Survival.

Abstract

Abstract The differentiation of naïve CD4+ T cells into discrete effector subsets, each able to mediate specific aspects of immunity is a central tenet of the adaptive immune response. Current dogma suggests that the generation of committed effector CD4+ T cells takes place over a 3–4 day period following initial engagement of the TCR. Activation of CD4+ T cells is thought to occur in three distinct functional phases, priming, proliferation and differentiation. Here, we present data indicating that CD4+ T cells acquire the disposition to commit to either Th1, Th2 or Treg lineages very soon after activation, prior to the induction of division. Further, we show that division is not required for the induction of a full program of differentiation to occur. We demonstrate that TCR signaling is responsible for two distinct activation programs whereby the strength of signal that a naïve T cell receives works in concert with cytokines at an early phase to induce differentiation, whereas the length of TCR signal can be construed as a secondary component of activation which controls the ability of CD4+ T cells to enter into division.