PubMed · 15250297
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Hirofumi Hasegawa, Yoshito Naiki. 2004. [Immune deficiency].. https://pubmed.ncbi.nlm.nih.gov/15250297/
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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.
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BACKGROUND/AIMS: Liver transplantation is an effective treatment for highly selected patients with hepatocellular carcinoma (HCC), but tumour recurrence remains an important cause of mortality. There are few data on the relation between the recurrence of HCC and lymphocytic infiltration following liver transplantation. METHODS: The tumour CD4+, CD8+, CD25+ and Foxp3+ lymphocyte infiltrate was assessed by immunohistochemistry in explant tissue of 69 patients who underwent liver transplantation for HCC between 1985 and 2001. The data were analysed according to HCC recurrence and factors known to be associated with outcome. RESULTS: Tumour size (Hazard ratio (95% CI: 1.19 (1.02, 1.39), P = 0.03)), vascular invasion (P = 0.02), lymphocyte infiltration (P = 0.02) and CD4:CD8 ratio (P = 0.001) were identified as significant univariate predictors of tumour recurrence. On multivariate analysis CD4:8 ratio (P = 0.001), vascular invasion (P = 0.01), tumour size (P = 0.06) and reduced lymphocyte infiltration (P = 0.03) were significant independent predictors of recurrence. The presence of Foxp3+ T-lymphocytes was not predictive of recurrence, but was associated with vascular invasion (FE = 9.02, P = 0.04). CONCLUSIONS: The data support the hypothesis that immune responses are important in HCC and that the phenotype of infiltrating lymphocytes is informative regarding prognosis.