Notch Governing Mature T Cell Differentiation

Abstract

The differentiation of naive T cells to effector/memory T cells is regulated by a variety of factors. The recent advance of the contribution of Notch signaling in this differentiation step has provided a new path to better understand the acquisition or persistence of effector function of mature T cells. In this review, we summarize emerging and, in some points, conflicting evidence for Notch signaling on mature T cell activation and differentiation.

Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells

“…Several recent reports suggest a role for the Notch pathway during differentiation of mature naïve T cells into functionally distinct effector T cell subsets in the periphery. Due to the complexity of potential Notch receptor/ligand interactions the molecular details of these processes are not yet clearly defined; a fact that is illustrated by a number of inconsistent reports published on the function of Notch in peripheral T cell activation and differentiation (reviewed in [11,40]). …”

Jagged1 and Delta1 Differentially Regulate the Outcome of Experimental Autoimmune Encephalomyelitis

“…There is a debate as to whether Notch signaling enhances T cell activation or suppresses T cell function in murine and human systems (38). Notch ligands have been shown to differentially affect T cell differentiation (16,(23)(24)(25), but the molecular events underlying the role of Notch in directing naive T cell differentiation toward the Th1, Th2, or Treg lineages are unclear.…”

Notch2 Signaling Is Required for Potent Antitumor Immunity In Vivo

“…Notch signaling controls mature T cell differentiation and activation by directly regulating transcription of effector molecules (7,8,14,15). In particular, our group has recently demonstrated that Notch2 signaling directly controls CTL effector molecules, including granzyme B, by integrating RBP-J and CREB1 (8).…”