Lack of T Cell Response to iPSC-Derived Retinal Pigment Epithelial Cells from HLA Homozygous Donors

Stem Cell Reports. 2016 Oct 11;7(4):619-634. doi: 10.1016/j.stemcr.2016.08.011. Epub 2016 Sep 15.

Abstract

Allografts of retinal pigment epithelial (RPE) cells have been considered for the treatment of ocular diseases. We recently started the transplantation of induced pluripotent stem cell (iPSC)-derived RPE cells for patients with age-related macular degeneration (autogenic grafts). However, there are at least two problems with this approach: (1) high cost, and (2) uselessness for acute patients. To resolve these issues, we established RPE cells from induced iPSCs in HLA homozygote donors. In vitro, human T cells directly recognized allogeneic iPSC-derived RPE cells that expressed HLA class I/II antigens. However, these T cells failed to respond to HLA-A, -B, and -DRB1-matched iPSC-derived RPE cells from HLA homozygous donors. Because of the lack of T cell response to iPSC-derived RPE cells from HLA homozygous donors, we can use these allogeneic iPSC-derived RPE cells in future clinical trials if the recipient and donor are HLA matched.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism*
  • Gene Expression
  • HLA Antigens / genetics*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Homozygote*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Inflammation Mediators / metabolism
  • Isoantigens / immunology
  • Retinal Pigment Epithelium / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tissue Donors

Substances

  • Cytokines
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Inflammation Mediators
  • Isoantigens