Immunomodulatory effect of bone marrow mesenchymal stem cells on T lymphocytes in patients with decompensated liver cirrhosis

Genet Mol Res. 2015 Jun 26;14(2):7039-46. doi: 10.4238/2015.June.26.13.

Abstract

We explored the immunomodulatory effects of bone marrow mesenchymal stem cells (BMSCs) on peripheral blood T lym-phocytes in patients with decompensation stage, hepatitis B-associated cirrhosis. MSCs from nine patients were analyzed by flow cytometry. Peripheral blood lymphocytes were isolated for fluorescent staining. Following stimulation by phytohemagglutinin (PHA), peripheral blood lymphocytes were co-cultured with BMSCs in serum and divided into four groups: (1) BMSC + lymphocyte + PHA contact culture group; (2) BMSC + lymphocyte + PHA non-contact culture group; (3) lym-phocyte + PHA positive control group; and (4) lymphocyte-only negative control group. Lymphocyte proliferation and frequencies of CD4(+)CD25(+)CD127(-) Tregs and CD4(+)CD8(-)IL-17(+) (Th17) cells were de-tected. Cell proliferation in groups 1 and 2 declined compared with group 3 (P < 0.01), and was notably higher than in group 4 (P < 0.01). CD4(+)CD25(+)CD127(-) Tregs frequencies in groups 1 and 2 were higher than in groups 3 and 4. In an intra-group comparison before and after culture, Th17 cell frequencies in groups 1 and 2 were higher than in group 4 (P < 0.01), but lower than in group 3 (P < 0.01). The Treg/Th17 ratio in groups 1 and 2 increased (P < 0.01), but did not change signifi-cantly in groups 3 and 4 (P > 0.05). In a comparison between groups after culture, the Treg/Th17 ratio in groups 1 and 2 increased more than in groups 3 and 4 (P < 0.01). BMSCs from cirrhotic patients can inhibit the proliferation of peripheral blood T lymphocytes, upregulate the ex-pression of CD4(+)CD25(+)CD127(-) Tregs, and improve Treg/Th17 imbal-ance. The mechanism by which this takes place may be associated with immunomodulatory effects induced by the secretion of soluble factors.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / pathology
  • Cell Proliferation
  • Coculture Techniques
  • Flow Cytometry
  • Gene Expression
  • Hepatitis B / complications
  • Hepatitis B / genetics
  • Hepatitis B / immunology*
  • Hepatitis B / pathology
  • Humans
  • Immunomodulation
  • Immunophenotyping
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / pathology
  • Lymphocyte Count
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / pathology
  • Phytohemagglutinins / pharmacology
  • Primary Cell Culture
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • Antigens, CD
  • Phytohemagglutinins