Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell.
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-beta1 (TGF-beta1), mainly contributed to the T cell suppression induced by CB-SC, as demonstrated by blocking experiments with a nitric oxide synthase inhibitor (Nomega-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.
Zhao
Yong
Y
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W. Polk Street, Chicago, IL 60612, USA. yongzhao@uic.edu
Huang
Zhihua
Z
Qi
Meirigeng
M
Lazzarini
Ping
P
Mazzone
Theodore
T
D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D010835:Phytohemagglutinins