CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection

Megan J. Welch; John R. Teijaro; Hanna A. Lewicki; Marco Colonna; Michael B.A. Oldstone

doi:10.1016/j.virol.2012.04.006

CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection

Megan J. Welch, John R. Teijaro, Hanna A. Lewicki, Marco Colonna, Michael B.A. Oldstone

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

DNAM-1 gene-deficient (-/-) mice take significantly longer to clear an acute and persistent LCMV infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 -/- mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 -/- and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 -/- CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the persistent viral infection.

Original language	English
Pages (from-to)	163-170
Number of pages	8
Journal	Virology
Volume	429
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2012.04.006
State	Published - Aug 1 2012

Keywords

Acute LCMV infection
DNAM-1 deficiency
Persistent LCMV infection
T cell defects

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10.1016/j.virol.2012.04.006

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title = "CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection",

abstract = "DNAM-1 gene-deficient (-/-) mice take significantly longer to clear an acute and persistent LCMV infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 -/- mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 -/- and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 -/- CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the persistent viral infection.",

keywords = "Acute LCMV infection, DNAM-1 deficiency, Persistent LCMV infection, T cell defects",

author = "Welch, {Megan J.} and Teijaro, {John R.} and Lewicki, {Hanna A.} and Marco Colonna and Oldstone, {Michael B.A.}",

note = "Funding Information: This is Publication no. 21239 from The Scripps Research Institute, La Jolla, California. This work was supported by NIH grant AI009484 (MBAO), NIH training grant AI007354 (JRT), and an award from the American Heart Association ( 11POST7430106 ) (JRT).",

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doi = "10.1016/j.virol.2012.04.006",

language = "English",

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T1 - CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection

AU - Welch, Megan J.

AU - Teijaro, John R.

AU - Lewicki, Hanna A.

AU - Colonna, Marco

AU - Oldstone, Michael B.A.

N1 - Funding Information: This is Publication no. 21239 from The Scripps Research Institute, La Jolla, California. This work was supported by NIH grant AI009484 (MBAO), NIH training grant AI007354 (JRT), and an award from the American Heart Association ( 11POST7430106 ) (JRT).

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N2 - DNAM-1 gene-deficient (-/-) mice take significantly longer to clear an acute and persistent LCMV infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 -/- mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 -/- and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 -/- CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the persistent viral infection.

AB - DNAM-1 gene-deficient (-/-) mice take significantly longer to clear an acute and persistent LCMV infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 -/- mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 -/- and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 -/- CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the persistent viral infection.

KW - Acute LCMV infection

KW - DNAM-1 deficiency

KW - Persistent LCMV infection

KW - T cell defects

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JO - Virology

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CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection

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Keywords

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