Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell

Abstract

Previous work identified a novel type of stem cell from human umbilical cord blood, designated cord blood-stem cells (CB-SC). To further evaluate their immune characteristics, we cocultured CB-SC with allogeneic peripheral blood lymphocytes in the presence of phytohaemagglutinin (PHA) or interleukin-2 (IL-2). Results showed that CB-SC could significantly inhibit lymphocyte proliferation and reduce tyrosine phosphorylation of STAT5 in both PHA- and IL-2-stimulated lymphocytes, along with the regulation on the phenotypes of CD4 + and CD8 + T cells. Additionally, CB-SC also suppressed the proliferation of IL-2-stimulated CD4 +CD25 + regulatory T cells. Mechanism studies revealed that programmed death receptor-1 ligand 1 (PD-L1) expressed on CB-SC membrane, together with a soluble factor nitric oxide (NO) released by PHA-stimulated CB-SC, not prostaglandin E2 (PGE2) and transforming growth factor-β1 (TGF-β1), mainly contributed to the T cell suppression induced by CB-SC, as demonstrated by blocking experiments with a nitric oxide synthase inhibitor ( N ω-nitro- l-arginine, l-NNA) and a neutralizing antibody to PD-L1. Our findings may advance our understanding of the immunobiology of stem cells and facilitate the therapeutic application of cord blood stem cells.