CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection

Christopher M. Snyder, Andrea Loewendorf, Elizabeth L. Bonnett, Michael Croft, Chris A. Benedict, Ann Hill

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8 + T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)3932-3941
Number of pages10
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009

Fingerprint

Muromegalovirus
Economic Inflation
Cytomegalovirus Infections
Epitopes
T-Lymphocytes
Infection
Inbred C57BL Mouse

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection. / Snyder, Christopher M.; Loewendorf, Andrea; Bonnett, Elizabeth L.; Croft, Michael; Benedict, Chris A.; Hill, Ann.

In: Journal of Immunology, Vol. 183, No. 6, 15.09.2009, p. 3932-3941.

Research output: Contribution to journalArticle

Snyder, Christopher M. ; Loewendorf, Andrea ; Bonnett, Elizabeth L. ; Croft, Michael ; Benedict, Chris A. ; Hill, Ann. / CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection. In: Journal of Immunology. 2009 ; Vol. 183, No. 6. pp. 3932-3941.
@article{3d8d50412253444db3665681276cb662,
title = "CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection",
abstract = "Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8 + T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.",
author = "Snyder, {Christopher M.} and Andrea Loewendorf and Bonnett, {Elizabeth L.} and Michael Croft and Benedict, {Chris A.} and Ann Hill",
year = "2009",
month = "9",
day = "15",
doi = "10.4049/jimmunol.0900227",
language = "English (US)",
volume = "183",
pages = "3932--3941",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection

AU - Snyder, Christopher M.

AU - Loewendorf, Andrea

AU - Bonnett, Elizabeth L.

AU - Croft, Michael

AU - Benedict, Chris A.

AU - Hill, Ann

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8 + T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.

AB - Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8 + T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.

UR - http://www.scopus.com/inward/record.url?scp=70349320168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349320168&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0900227

DO - 10.4049/jimmunol.0900227

M3 - Article

C2 - 19692644

AN - SCOPUS:70349320168

VL - 183

SP - 3932

EP - 3941

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -