Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes

Senji Kasahara, Kazuki Ando, Kuniaki Saito, Kenji Sekikawa, Hiroyasu Ito, Tetsuya Ishikawa, Hiroo Ohnishi, Mitsuru Seishima, Shinichi Kakumu, Hisataka Moriwaki

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Recent studies have shown that tumor necrosis factor alpha (TNF-α) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-α knockout (TNF-α-/- mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-α-/- mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-α-/- mice after two sessions of immunization with the HBV plasmid; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α-/- mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-α enhanced the proliferation of a TNF-α-/- clone but suppressed that of a TNF-α+/+ clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.

Original languageEnglish
Pages (from-to)2469-2476
Number of pages8
JournalJournal of Virology
Volume77
Issue number4
DOIs
Publication statusPublished - 01-02-2003

Fingerprint

cytotoxic T-lymphocytes
Hepatitis B virus
Cytotoxic T-Lymphocytes
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha
Clone Cells
clones
mice
Immunization
plasmids
immunization
Plasmids
Lymphoid Tissue
dendritic cells
Hepatitis B Surface Antigens
cell differentiation
Dendritic Cells
stem cells
cytotoxicity
Cell Differentiation

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kasahara, Senji ; Ando, Kazuki ; Saito, Kuniaki ; Sekikawa, Kenji ; Ito, Hiroyasu ; Ishikawa, Tetsuya ; Ohnishi, Hiroo ; Seishima, Mitsuru ; Kakumu, Shinichi ; Moriwaki, Hisataka. / Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes. In: Journal of Virology. 2003 ; Vol. 77, No. 4. pp. 2469-2476.
@article{458384676e7c4d42926e91276dc0bc2c,
title = "Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes",
abstract = "Recent studies have shown that tumor necrosis factor alpha (TNF-α) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-α knockout (TNF-α-/- mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-α-/- mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-α-/- mice after two sessions of immunization with the HBV plasmid; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α-/- mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-α enhanced the proliferation of a TNF-α-/- clone but suppressed that of a TNF-α+/+ clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.",
author = "Senji Kasahara and Kazuki Ando and Kuniaki Saito and Kenji Sekikawa and Hiroyasu Ito and Tetsuya Ishikawa and Hiroo Ohnishi and Mitsuru Seishima and Shinichi Kakumu and Hisataka Moriwaki",
year = "2003",
month = "2",
day = "1",
doi = "10.1128/JVI.77.4.2469-2476.2003",
language = "English",
volume = "77",
pages = "2469--2476",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

Kasahara, S, Ando, K, Saito, K, Sekikawa, K, Ito, H, Ishikawa, T, Ohnishi, H, Seishima, M, Kakumu, S & Moriwaki, H 2003, 'Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes', Journal of Virology, vol. 77, no. 4, pp. 2469-2476. https://doi.org/10.1128/JVI.77.4.2469-2476.2003

Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes. / Kasahara, Senji; Ando, Kazuki; Saito, Kuniaki; Sekikawa, Kenji; Ito, Hiroyasu; Ishikawa, Tetsuya; Ohnishi, Hiroo; Seishima, Mitsuru; Kakumu, Shinichi; Moriwaki, Hisataka.

In: Journal of Virology, Vol. 77, No. 4, 01.02.2003, p. 2469-2476.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes

AU - Kasahara, Senji

AU - Ando, Kazuki

AU - Saito, Kuniaki

AU - Sekikawa, Kenji

AU - Ito, Hiroyasu

AU - Ishikawa, Tetsuya

AU - Ohnishi, Hiroo

AU - Seishima, Mitsuru

AU - Kakumu, Shinichi

AU - Moriwaki, Hisataka

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Recent studies have shown that tumor necrosis factor alpha (TNF-α) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-α knockout (TNF-α-/- mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-α-/- mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-α-/- mice after two sessions of immunization with the HBV plasmid; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α-/- mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-α enhanced the proliferation of a TNF-α-/- clone but suppressed that of a TNF-α+/+ clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.

AB - Recent studies have shown that tumor necrosis factor alpha (TNF-α) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-α knockout (TNF-α-/- mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-α-/- mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-α-/- mice after two sessions of immunization with the HBV plasmid; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α-/- mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-α enhanced the proliferation of a TNF-α-/- clone but suppressed that of a TNF-α+/+ clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.

UR - http://www.scopus.com/inward/record.url?scp=0037320085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037320085&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.4.2469-2476.2003

DO - 10.1128/JVI.77.4.2469-2476.2003

M3 - Article

C2 - 12551985

AN - SCOPUS:0037320085

VL - 77

SP - 2469

EP - 2476

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

ER -