Adoptive transfer of genetically engineered WT1-specific cytotoxic T lymphocytes does not induce renal injury

J Hematol Oncol. 2014 Jan 6:7:3. doi: 10.1186/1756-8722-7-3.

Abstract

Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic. However, concern of this therapy still remains, since WT1 is abundantly expressed in renal glomerular podocytes. In the present study, we clearly showed that WT1-specific cytotoxic T lymphocytes (CTLs) certainly exerted cytotoxicity against podocytes in vitro; however, they did not damage podocytes in vivo. This might be due to the anatomical localization of podocytes, being structurally separated from circulating CTLs in glomerular capillaries by an exceptionally thick basement membrane.

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Cell Line
  • Cytotoxicity, Immunologic / immunology
  • Flow Cytometry
  • Genetic Engineering
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology
  • HLA-A24 Antigen / metabolism
  • Humans
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / metabolism
  • Mice
  • Mice, Transgenic
  • Podocytes / immunology
  • Podocytes / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / transplantation*
  • WT1 Proteins / genetics
  • WT1 Proteins / immunology*
  • WT1 Proteins / metabolism

Substances

  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • WT1 Proteins