Transmission of survival signals through Delta-like 1 on activated CD4⁺ T cells.

ABSTRACT: Notch expressed on CD4⁺ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4⁺ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4⁺ T cells from Dll1^-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4⁺ T cells from Dll1^-/- mice compared with control cells. Dll1^-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4⁺ T cells from Dll1^-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4⁺ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4⁺ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses.

SUBMITTER: Furukawa T 

PROVIDER: S-EPMC5034251 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature