Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-γ production in BALB/c mice infected with Mycobacterium avium

Seung H. Kim, Dae Ho Cho, Tae Sung Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-γ. Treatment with anti-IFN-γ antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-γ in CD4+ T cells.

Original languageEnglish
Pages (from-to)3365-3373
Number of pages9
JournalVaccine
Volume24
Issue number16
DOIs
Publication statusPublished - 2006 Apr 12

Fingerprint

interleukin-18
Mycobacterium avium
Single-Chain Antibodies
Interleukin-18
interferons
Interferons
DNA
mice
Mycobacterium Infections
lungs
Lung
Immunization
immunization
T-lymphocytes
infection
T-Lymphocytes
Th1 Cells
Bacterial Load
cell-mediated immunity
nitric oxide

Keywords

  • CD3 T cell
  • Fusion DNA
  • IL-18
  • Immunity
  • Mycobacterium avium

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

@article{af747402cf9d4008b03a07b7ed050543,
title = "Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-γ production in BALB/c mice infected with Mycobacterium avium",
abstract = "T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-γ. Treatment with anti-IFN-γ antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-γ in CD4+ T cells.",
keywords = "CD3 T cell, Fusion DNA, IL-18, Immunity, Mycobacterium avium",
author = "Kim, {Seung H.} and Cho, {Dae Ho} and Kim, {Tae Sung}",
year = "2006",
month = "4",
day = "12",
doi = "10.1016/j.vaccine.2005.12.065",
language = "English",
volume = "24",
pages = "3365--3373",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "16",

}

TY - JOUR

T1 - Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-γ production in BALB/c mice infected with Mycobacterium avium

AU - Kim, Seung H.

AU - Cho, Dae Ho

AU - Kim, Tae Sung

PY - 2006/4/12

Y1 - 2006/4/12

N2 - T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-γ. Treatment with anti-IFN-γ antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-γ in CD4+ T cells.

AB - T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-γ. Treatment with anti-IFN-γ antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-γ in CD4+ T cells.

KW - CD3 T cell

KW - Fusion DNA

KW - IL-18

KW - Immunity

KW - Mycobacterium avium

UR - http://www.scopus.com/inward/record.url?scp=33645069658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645069658&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2005.12.065

DO - 10.1016/j.vaccine.2005.12.065

M3 - Article

VL - 24

SP - 3365

EP - 3373

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 16

ER -