Roles of T Lymphocytes in Defense against Experimental Acute Pulmonary Infection of Mice with Murine Cytomegalovirus

Genki Kimura, Hiroaki Takimoto, Hiroki Yoshida, Toshiharu Ninomiya, Qijie Chen, Masumi Ohtsu, Kikuo Nomoto

Research output: Contribution to journalArticle

Abstract

The aim of this study together with the preceding study (Kimura et al., Biomed. Res. 21(3), 145-163, 2000) is to reveal the sequential barrier of host-defense factors to experimental acute pulmonary infection of mice with murine cytomegalovirus. Time course of virus load in lungs following an intratracheal inoculation with the virus was divided into 4 phases: the inoculum-decreasing, phase I (0 h post-infection (p.i.)-18h p.i.), the virus-load increasing, phase II (24h p.i.-48h p.i.), the plateau of virus-load, phase III (2d p.i.-14d p. i.), and the slow virus-clearance, phase IV (14d p.i.-24d-28d p.i.). The viral-antigen producing cells were detectable in phase III exclusively in the cavity side of alveoli in the histological sections of lungs. There was no histologically detectable inflammation both in the alveolar cavity and in the interstitium of the lungs. The number of T cells recoverable from lungs increased only to a small extent both in whole lungs and in the bronchoalveolar space. CD8+ T cells isolated from whole lungs during the period of time spanning 5d p.i.-21d p.i., however, had a readily-detectable immediate ex vivo CTL activity specific to the known dominant epitope in the immediately early gene product of the virus and a fraction of 20–40% of CD8+ T cells were producing IFN-γ. The results of in vivo cell-depletion and cytokine-depletion experiments suggest that each of CD4+ T cells and CD8+ T cells alone play a role in the slow but substantial reduction of virus load in the lungs and that IFN-γ also plays an antiviral role in phase IV. The results of double depletion experiments suggest that CD4+ T cells and CD8+ T cells synergistically play roles in prevention of a progressive increase in virus load in lungs beyond the plateau caused by expansion of the infection sites in the alveolar cavities and by infection of the interstitium of the lung. Taking together with the results of the preceding study, we suggest the frame of the sequential barrier to the primary pulmonary infection with the virus as follows. Phase I, alveolar macrophages; phase II, alveolar macrophages; the early phase III, alveolar macrophages; the late phase III, alveolar macrophages, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in combination; and phase IV, CD4+ T cells alone, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in vombination. We suggest that, in defense against infection of the lung with a slowly-reproducing and mildly-cytotoxic virus like murine cytomegalovirus, a nonspecific defense fatcor with a low tissue-toxicity like macrophages plays more important role than an antigen-specific and clonal-expansion dependent defense factor like T cells, in order to avoid a life-threatening obstruction of normal functioning of the lung due to long-lasting inflammation.

Original languageEnglish
Pages (from-to)225-246
Number of pages22
JournalBiomedical Research (Japan)
Volume21
Issue number5
DOIs
Publication statusPublished - Jan 1 2000

Fingerprint

Muromegalovirus
T-cells
T-Lymphocytes
Viruses
Lung
Infection
Alveolar Macrophages
Virus Diseases
Inflammation
TCF Transcription Factors
Viral Antigens
Macrophages

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Roles of T Lymphocytes in Defense against Experimental Acute Pulmonary Infection of Mice with Murine Cytomegalovirus. / Kimura, Genki; Takimoto, Hiroaki; Yoshida, Hiroki; Ninomiya, Toshiharu; Chen, Qijie; Ohtsu, Masumi; Nomoto, Kikuo.

In: Biomedical Research (Japan), Vol. 21, No. 5, 01.01.2000, p. 225-246.

Research output: Contribution to journalArticle

Kimura, Genki ; Takimoto, Hiroaki ; Yoshida, Hiroki ; Ninomiya, Toshiharu ; Chen, Qijie ; Ohtsu, Masumi ; Nomoto, Kikuo. / Roles of T Lymphocytes in Defense against Experimental Acute Pulmonary Infection of Mice with Murine Cytomegalovirus. In: Biomedical Research (Japan). 2000 ; Vol. 21, No. 5. pp. 225-246.
@article{473a545263784027814ae568cf059533,
title = "Roles of T Lymphocytes in Defense against Experimental Acute Pulmonary Infection of Mice with Murine Cytomegalovirus",
abstract = "The aim of this study together with the preceding study (Kimura et al., Biomed. Res. 21(3), 145-163, 2000) is to reveal the sequential barrier of host-defense factors to experimental acute pulmonary infection of mice with murine cytomegalovirus. Time course of virus load in lungs following an intratracheal inoculation with the virus was divided into 4 phases: the inoculum-decreasing, phase I (0 h post-infection (p.i.)-18h p.i.), the virus-load increasing, phase II (24h p.i.-48h p.i.), the plateau of virus-load, phase III (2d p.i.-14d p. i.), and the slow virus-clearance, phase IV (14d p.i.-24d-28d p.i.). The viral-antigen producing cells were detectable in phase III exclusively in the cavity side of alveoli in the histological sections of lungs. There was no histologically detectable inflammation both in the alveolar cavity and in the interstitium of the lungs. The number of T cells recoverable from lungs increased only to a small extent both in whole lungs and in the bronchoalveolar space. CD8+ T cells isolated from whole lungs during the period of time spanning 5d p.i.-21d p.i., however, had a readily-detectable immediate ex vivo CTL activity specific to the known dominant epitope in the immediately early gene product of the virus and a fraction of 20–40{\%} of CD8+ T cells were producing IFN-γ. The results of in vivo cell-depletion and cytokine-depletion experiments suggest that each of CD4+ T cells and CD8+ T cells alone play a role in the slow but substantial reduction of virus load in the lungs and that IFN-γ also plays an antiviral role in phase IV. The results of double depletion experiments suggest that CD4+ T cells and CD8+ T cells synergistically play roles in prevention of a progressive increase in virus load in lungs beyond the plateau caused by expansion of the infection sites in the alveolar cavities and by infection of the interstitium of the lung. Taking together with the results of the preceding study, we suggest the frame of the sequential barrier to the primary pulmonary infection with the virus as follows. Phase I, alveolar macrophages; phase II, alveolar macrophages; the early phase III, alveolar macrophages; the late phase III, alveolar macrophages, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in combination; and phase IV, CD4+ T cells alone, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in vombination. We suggest that, in defense against infection of the lung with a slowly-reproducing and mildly-cytotoxic virus like murine cytomegalovirus, a nonspecific defense fatcor with a low tissue-toxicity like macrophages plays more important role than an antigen-specific and clonal-expansion dependent defense factor like T cells, in order to avoid a life-threatening obstruction of normal functioning of the lung due to long-lasting inflammation.",
author = "Genki Kimura and Hiroaki Takimoto and Hiroki Yoshida and Toshiharu Ninomiya and Qijie Chen and Masumi Ohtsu and Kikuo Nomoto",
year = "2000",
month = "1",
day = "1",
doi = "10.2220/biomedres.21.225",
language = "English",
volume = "21",
pages = "225--246",
journal = "Biomedical Research",
issn = "0388-6107",
publisher = "Biomedical Research Foundation",
number = "5",

}

TY - JOUR

T1 - Roles of T Lymphocytes in Defense against Experimental Acute Pulmonary Infection of Mice with Murine Cytomegalovirus

AU - Kimura, Genki

AU - Takimoto, Hiroaki

AU - Yoshida, Hiroki

AU - Ninomiya, Toshiharu

AU - Chen, Qijie

AU - Ohtsu, Masumi

AU - Nomoto, Kikuo

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The aim of this study together with the preceding study (Kimura et al., Biomed. Res. 21(3), 145-163, 2000) is to reveal the sequential barrier of host-defense factors to experimental acute pulmonary infection of mice with murine cytomegalovirus. Time course of virus load in lungs following an intratracheal inoculation with the virus was divided into 4 phases: the inoculum-decreasing, phase I (0 h post-infection (p.i.)-18h p.i.), the virus-load increasing, phase II (24h p.i.-48h p.i.), the plateau of virus-load, phase III (2d p.i.-14d p. i.), and the slow virus-clearance, phase IV (14d p.i.-24d-28d p.i.). The viral-antigen producing cells were detectable in phase III exclusively in the cavity side of alveoli in the histological sections of lungs. There was no histologically detectable inflammation both in the alveolar cavity and in the interstitium of the lungs. The number of T cells recoverable from lungs increased only to a small extent both in whole lungs and in the bronchoalveolar space. CD8+ T cells isolated from whole lungs during the period of time spanning 5d p.i.-21d p.i., however, had a readily-detectable immediate ex vivo CTL activity specific to the known dominant epitope in the immediately early gene product of the virus and a fraction of 20–40% of CD8+ T cells were producing IFN-γ. The results of in vivo cell-depletion and cytokine-depletion experiments suggest that each of CD4+ T cells and CD8+ T cells alone play a role in the slow but substantial reduction of virus load in the lungs and that IFN-γ also plays an antiviral role in phase IV. The results of double depletion experiments suggest that CD4+ T cells and CD8+ T cells synergistically play roles in prevention of a progressive increase in virus load in lungs beyond the plateau caused by expansion of the infection sites in the alveolar cavities and by infection of the interstitium of the lung. Taking together with the results of the preceding study, we suggest the frame of the sequential barrier to the primary pulmonary infection with the virus as follows. Phase I, alveolar macrophages; phase II, alveolar macrophages; the early phase III, alveolar macrophages; the late phase III, alveolar macrophages, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in combination; and phase IV, CD4+ T cells alone, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in vombination. We suggest that, in defense against infection of the lung with a slowly-reproducing and mildly-cytotoxic virus like murine cytomegalovirus, a nonspecific defense fatcor with a low tissue-toxicity like macrophages plays more important role than an antigen-specific and clonal-expansion dependent defense factor like T cells, in order to avoid a life-threatening obstruction of normal functioning of the lung due to long-lasting inflammation.

AB - The aim of this study together with the preceding study (Kimura et al., Biomed. Res. 21(3), 145-163, 2000) is to reveal the sequential barrier of host-defense factors to experimental acute pulmonary infection of mice with murine cytomegalovirus. Time course of virus load in lungs following an intratracheal inoculation with the virus was divided into 4 phases: the inoculum-decreasing, phase I (0 h post-infection (p.i.)-18h p.i.), the virus-load increasing, phase II (24h p.i.-48h p.i.), the plateau of virus-load, phase III (2d p.i.-14d p. i.), and the slow virus-clearance, phase IV (14d p.i.-24d-28d p.i.). The viral-antigen producing cells were detectable in phase III exclusively in the cavity side of alveoli in the histological sections of lungs. There was no histologically detectable inflammation both in the alveolar cavity and in the interstitium of the lungs. The number of T cells recoverable from lungs increased only to a small extent both in whole lungs and in the bronchoalveolar space. CD8+ T cells isolated from whole lungs during the period of time spanning 5d p.i.-21d p.i., however, had a readily-detectable immediate ex vivo CTL activity specific to the known dominant epitope in the immediately early gene product of the virus and a fraction of 20–40% of CD8+ T cells were producing IFN-γ. The results of in vivo cell-depletion and cytokine-depletion experiments suggest that each of CD4+ T cells and CD8+ T cells alone play a role in the slow but substantial reduction of virus load in the lungs and that IFN-γ also plays an antiviral role in phase IV. The results of double depletion experiments suggest that CD4+ T cells and CD8+ T cells synergistically play roles in prevention of a progressive increase in virus load in lungs beyond the plateau caused by expansion of the infection sites in the alveolar cavities and by infection of the interstitium of the lung. Taking together with the results of the preceding study, we suggest the frame of the sequential barrier to the primary pulmonary infection with the virus as follows. Phase I, alveolar macrophages; phase II, alveolar macrophages; the early phase III, alveolar macrophages; the late phase III, alveolar macrophages, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in combination; and phase IV, CD4+ T cells alone, CD8+ T cells alone, and CD4+ T cells and CD8+ T cells in vombination. We suggest that, in defense against infection of the lung with a slowly-reproducing and mildly-cytotoxic virus like murine cytomegalovirus, a nonspecific defense fatcor with a low tissue-toxicity like macrophages plays more important role than an antigen-specific and clonal-expansion dependent defense factor like T cells, in order to avoid a life-threatening obstruction of normal functioning of the lung due to long-lasting inflammation.

UR - http://www.scopus.com/inward/record.url?scp=85024448061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024448061&partnerID=8YFLogxK

U2 - 10.2220/biomedres.21.225

DO - 10.2220/biomedres.21.225

M3 - Article

AN - SCOPUS:85024448061

VL - 21

SP - 225

EP - 246

JO - Biomedical Research

JF - Biomedical Research

SN - 0388-6107

IS - 5

ER -