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

Research output: Contribution to journalArticle

42 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
Externally publishedYes

Fingerprint

CD8 Antigens
Cytotoxic T-Lymphocytes
Human Herpesvirus 4
Stomach
Carcinoma
HLA Antigens
Tumor-Infiltrating Lymphocytes
Histocompatibility Antigens Class I
Proteins
Vaccinia virus
Phytohemagglutinins
T-Cell Antigen Receptor
Cultured Cells
Adenocarcinoma
Fibroblasts
Lymphocytes
T-Lymphocytes
Peptides

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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

In: Journal of Clinical Investigation, Vol. 104, No. 2, 07.1999, p. 163-171.

Research output: Contribution to journalArticle

Kuzushima, Kiyotaka ; Nakamura, Shigeo ; Nakamura, Tsuneya ; Yamamura, Yoshitaka ; Yokoyama, Naoaki ; Fujita, Masatoshi ; Kiyono, Tohru ; Tsurumi, Tatsuya. / Increased frequency of antigen-specific CD8+ cytotoxic T lymphocytes infiltrating an epstein-barr virus-associated gastric carcinoma. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 2. pp. 163-171.
@article{f2e47c58fe8442a0af744e63c1b97244,
title = "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 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.",
author = "Kiyotaka Kuzushima and Shigeo Nakamura and Tsuneya Nakamura and Yoshitaka Yamamura and Naoaki Yokoyama and Masatoshi Fujita and Tohru Kiyono and Tatsuya Tsurumi",
year = "1999",
month = "7",
doi = "10.1172/JCI6062",
language = "English",
volume = "104",
pages = "163--171",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

TY - JOUR

T1 - Increased frequency of antigen-specific CD8+ cytotoxic T lymphocytes infiltrating an epstein-barr virus-associated gastric carcinoma

AU - Kuzushima, Kiyotaka

AU - Nakamura, Shigeo

AU - Nakamura, Tsuneya

AU - Yamamura, Yoshitaka

AU - Yokoyama, Naoaki

AU - Fujita, Masatoshi

AU - Kiyono, Tohru

AU - Tsurumi, Tatsuya

PY - 1999/7

Y1 - 1999/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032732363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032732363&partnerID=8YFLogxK

U2 - 10.1172/JCI6062

DO - 10.1172/JCI6062

M3 - Article

C2 - 10411545

AN - SCOPUS:0032732363

VL - 104

SP - 163

EP - 171

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

ER -