Increased frequency of antigen-specific CD8+ cytotoxic T lymphocytes infiltrating an Epstein-Barr virus–associated gastric carcinoma
Kiyotaka Kuzushima, Shigeo Nakamura, Tsuneya Nakamura, Yoshitaka Yamamura, Naoaki Yokoyama, Masatoshi Fujita, Tohru Kiyono, Tatsuya Tsurumi
Kiyotaka Kuzushima, Shigeo Nakamura, Tsuneya Nakamura, Yoshitaka Yamamura, Naoaki Yokoyama, Masatoshi Fujita, Tohru Kiyono, Tatsuya Tsurumi
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Increased frequency of antigen-specific CD8+ cytotoxic T lymphocytes infiltrating an Epstein-Barr virus–associated gastric carcinoma

Abstract

Gastric adenocarcinomas carrying Epstein-Barr virus (EBV) are known to be accompanied by massive lymphocyte infiltration. To characterize the tumor-infiltrating lymphocytes (TILs), we isolated and cultured such cells from a surgically resected EBV-associated gastric carcinoma. They were found to be positive for CD3, CD8, T-cell receptor β chain, and cytotoxic molecules. The isolated TILs consisted of human leukocyte antigen (HLA) class I–restricted CD8+ cytotoxic T lymphocytes (CTLs), which killed autologous EBV-transformed cells (but not phytohemagglutinin blast cells) and recognized HLA-A24 as restriction molecules. However, the TILs did not recognize known EBV antigenic peptides presented by HLA-A24 molecules, nor HLA-A24+ fibroblasts infected with vaccinia recombinant virus expressing each of the EBV latent proteins. EBV+ gastric carcinomas do not express conventional target proteins of EBV-specific CTLs, and the data suggest that some cellular proteins may be involved in the strong T-cell response to EBV-associated gastric carcinoma. In addition, our data suggest that class I–restricted, antigen-specific CD8+ CTLs are specifically expanded within EBV+ gastric carcinoma tissue.

Authors

Kiyotaka Kuzushima, Shigeo Nakamura, Tsuneya Nakamura, Yoshitaka Yamamura, Naoaki Yokoyama, Masatoshi Fujita, Tohru Kiyono, Tatsuya Tsurumi

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(a) Cytotoxicity toward autologous LCLs of TILs (filled circles) and IL-...
(a) Cytotoxicity toward autologous LCLs of TILs (filled circles) and IL-2–activated PBMCs (filled squares). (b) Precursor frequency of antigen-specific CD8+ CTLs reactive to autologous LCLs in TILs (filled circles) and in PBMCs (open circles), as determined by LDA.