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

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44 Citations (Scopus)

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 maybe 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.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number2
DOIs
Publication statusPublished - Jul 1999

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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