Contribution of virus-specific CD8+ cytotoxic T cells to virus clearance or pathologic manifestations of influenza virus infection in a T cell receptor transgenic mouse model

Dimitrios Moskofidis, Dimitris Kioussis

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147 Citations (Scopus)

Abstract

The ability of influenza virus to evade immune surveillance by neutralizing antibodies (Abs) directed against its variable surface antigens provides a challenge to the development of effective vaccines. CD8+ cytotoxic T lymphocytes (CTLs) restricted by class I major histocompatibility complex molecules are important in establishing immunity to influenza virus because they recognize internal viral proteins which are conserved between multiple viral strains. In contrast, protective Abs are strain-specific. However, the precise role of effector CD8+ CTLs in protection from influenza virus infection, critical for understanding disease pathogenesis, has not been well defined. In transgenic mice with a very high frequency of antiinfluenza CTL precursors, but without protective Abs, CD8+ CTLs conferred protection against low dose viral challenge, but exacerbated viral pathology and caused mortality at high viral dose. The data suggest a dual role for CD8+ CTLs against influenza, which may present a challenge to the development of effective CTL vaccines. Effector mechanisms used by CD8+ CTLs in orchestrating clearance of virus and recovery from experimental influenza infection, or potentiation of lethal pathology, are discussed.

Original languageEnglish (US)
Pages (from-to)223-232
Number of pages10
JournalJournal of Experimental Medicine
Volume188
Issue number2
DOIs
StatePublished - Jul 20 1998

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Cytotoxic T-Lymphocytes
Virus Diseases
T-Cell Antigen Receptor
Orthomyxoviridae
Transgenic Mice
Viruses
T-Lymphocytes
Human Influenza
Vaccines
Pathology
Antibodies
Viral Proteins
Surface Antigens
Neutralizing Antibodies
Major Histocompatibility Complex
Immunity
Mortality
Infection

Keywords

  • CD8 cytotoxic T lymphocytes
  • Influenza A virus
  • Influenza viral pneumonia
  • Interferon γ
  • T cell receptor- transgenic mice

ASJC Scopus subject areas

  • Immunology

Cite this

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N2 - The ability of influenza virus to evade immune surveillance by neutralizing antibodies (Abs) directed against its variable surface antigens provides a challenge to the development of effective vaccines. CD8+ cytotoxic T lymphocytes (CTLs) restricted by class I major histocompatibility complex molecules are important in establishing immunity to influenza virus because they recognize internal viral proteins which are conserved between multiple viral strains. In contrast, protective Abs are strain-specific. However, the precise role of effector CD8+ CTLs in protection from influenza virus infection, critical for understanding disease pathogenesis, has not been well defined. In transgenic mice with a very high frequency of antiinfluenza CTL precursors, but without protective Abs, CD8+ CTLs conferred protection against low dose viral challenge, but exacerbated viral pathology and caused mortality at high viral dose. The data suggest a dual role for CD8+ CTLs against influenza, which may present a challenge to the development of effective CTL vaccines. Effector mechanisms used by CD8+ CTLs in orchestrating clearance of virus and recovery from experimental influenza infection, or potentiation of lethal pathology, are discussed.

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