Characteristic expression of major histocompatibility complex and immune privilege genes in human pluripotent stem cells and their derivatives

Hsin Fu Chen, Chun Ying Yu, Mei Jou Chen, Shiu Huey Chou, Ming Shan Chiang, Wen Hsi Chou, Bor Sheng Ko, Hsiang Po Huang, Hung Chih Kuo, Hong Nerng Ho

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16 Citations (Scopus)

Abstract

Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have been regarded as useful sources for cell-based transplantation therapy. However, immunogenicity of the cells remains the major determinant for successful clinical application. We report the examination of several hESC lines (NTU1 and H9), hiPSC lines, and their derivatives (including stem cell-derived hepatocytes) for the expression of major histocompatibility complex (MHC), natural killer (NK) cell receptor (NKp30, NKp44, NKp46) ligand, immune-related genes, human leukocyte antigen (HLA) haplotyping, and the effects in functional mixed lymphocyte reaction (MLR). Flow cytometry showed lower levels (percentages and fluorescence intensities) of MHC class I (MHC-I) molecules, b2-microglobulin, and HLA-E in undifferentiated stem cells. The levels were increased after cotreatment with interferon-g and/or in vitro differentiation. Antigen-presenting cell markers (CD11c, CD80, and CD86) and MHC-II (HLA-DP, -DQ, and -DR) remained low throughout the treatments. Recognition of stem cells/derivatives by NK lysis receptors were lower or absent. Activation of responder lymphocytes was significantly lower by undifferentiated stem cells than by allogeneic lymphocytes in MLR, but differentiated NTU1 hESCs induced a cell number-dependent lymphocyte proliferation comparable with that by allogeneic lymphocytes. Interestingly, activation of lymphocytes by differentiated hiPSCs or H9 cells became blunted at higher cell numbers. Real-time reverse transcriptase PCR (RT-PCR) showed significant differential expression of immune privilege genes (TGF-b2, Arginase 2, Indole 1, GATA3, POMC, VIP, CALCA, CALCB, IL-1RN, CD95L, CR1L, Serpine 1, HMOX1, IL6, LGALS3, HEBP1, THBS1, CD59, and LGALS1) in plurip-otent stem cells/derivatives when compared to somatic cells. It was concluded that pluripotent stem cells/derivatives are predicted to be immunogenic, though evidence suggests some level of potential immune privilege. In addition, differential immunogenicity may exist between different pluripotent stem cell lines and their derivatives.

Original languageEnglish
Pages (from-to)845-864
Number of pages20
JournalCell Transplantation
Volume24
Issue number5
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Embryonic stem cells
  • Immune privilege
  • Immunogenicity
  • Induced pluripotent stem cells
  • Major histocompatibility complex (MHC)
  • Pluripotent stem cells

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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