CD4+CD25− T Cells That Express Latency-Associated Peptide on the Surface Suppress CD4+CD45RBhigh-Induced Colitis by a TGF-β-Dependent Mechanism

Abstract

Abstract Murine CD4+CD25+ regulatory cells have been reported to express latency-associated peptide (LAP) and TGF-β on the surface after activation, and exert regulatory function by the membrane-bound TGF-β in vitro. We have now found that a small population of CD4+ T cells, both CD25+ and CD25−, can be stained with a goat anti-LAP polyclonal Ab without being stimulated. Virtually all these LAP+ cells are also positive for thrombospondin, which has the ability to convert latent TGF-β to the active form. In the CD4+CD45RBhigh-induced colitis model of SCID mice, regulatory activity was exhibited not only by CD25+LAP+ and CD25+LAP− cells, but also by CD25−LAP+ cells. CD4+CD25−LAP+ T cells were part of the CD45RBlow cell fraction. CD4+CD25−LAP−CD45RBlow cells had minimal, if any, regulatory activity in the colitis model. The regulatory function of CD25−LAP+ cells was abrogated in vivo by anti-TGF-β mAb. These results identify a new TGF-β-dependent regulatory CD4+ T cell phenotype that is CD25− and LAP+.

Key Biomarkers

Symptom Clusters