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.
Highlights
Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic
In the present series of experiments, we examined in detail the cytotoxic effect of WT1-specific cytotoxic T lymphocytes (CTLs) against podocytes using in vitro and in vivo systems
WT1-specific CTLs did not show cytotoxicity against WT1 peptide-loaded or -unloaded MPC-5. These results showed that WT1-specific CTLs can lyse podocytes in an HLA-restricted manner through recognition of the WT1 epitope that is naturally processed from WT1 protein in podocytes and presented on the cell surface in the context of HLA class I molecules
Summary
Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic. Concern of this therapy still remains, since WT1 is abundantly expressed in renal glomerular podocytes. We clearly showed that WT1-specific cytotoxic T lymphocytes (CTLs) certainly exerted cytotoxicity against podocytes in vitro; 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
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