CD4 T cell-mediated protection from lethal influenza

Perform and antibody-mediated mechanisms give a one-two punch

Deborah M Brown, Allison M. Dilzer, Dana L. Meents, Susan L. Swain

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-γ or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perform (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

Original languageEnglish (US)
Pages (from-to)2888-2898
Number of pages11
JournalJournal of Immunology
Volume177
Issue number5
StatePublished - Sep 1 2006

Fingerprint

Cytoprotection
Human Influenza
T-Lymphocytes
Antibodies
B-Lymphocytes
Infection
Orthomyxoviridae
Immune Sera
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

CD4 T cell-mediated protection from lethal influenza : Perform and antibody-mediated mechanisms give a one-two punch. / Brown, Deborah M; Dilzer, Allison M.; Meents, Dana L.; Swain, Susan L.

In: Journal of Immunology, Vol. 177, No. 5, 01.09.2006, p. 2888-2898.

Research output: Contribution to journalArticle

Brown, Deborah M ; Dilzer, Allison M. ; Meents, Dana L. ; Swain, Susan L. / CD4 T cell-mediated protection from lethal influenza : Perform and antibody-mediated mechanisms give a one-two punch. In: Journal of Immunology. 2006 ; Vol. 177, No. 5. pp. 2888-2898.
@article{3aaa75ef3bd04f49892a2435738b9eee,
title = "CD4 T cell-mediated protection from lethal influenza: Perform and antibody-mediated mechanisms give a one-two punch",
abstract = "The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-γ or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perform (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.",
author = "Brown, {Deborah M} and Dilzer, {Allison M.} and Meents, {Dana L.} and Swain, {Susan L.}",
year = "2006",
month = "9",
day = "1",
language = "English (US)",
volume = "177",
pages = "2888--2898",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - CD4 T cell-mediated protection from lethal influenza

T2 - Perform and antibody-mediated mechanisms give a one-two punch

AU - Brown, Deborah M

AU - Dilzer, Allison M.

AU - Meents, Dana L.

AU - Swain, Susan L.

PY - 2006/9/1

Y1 - 2006/9/1

N2 - The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-γ or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perform (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

AB - The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-γ or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perform (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

UR - http://www.scopus.com/inward/record.url?scp=33747765545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747765545&partnerID=8YFLogxK

M3 - Article

VL - 177

SP - 2888

EP - 2898

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -