T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice

J Virol. 2010 Sep;84(18):9318-25. doi: 10.1128/JVI.01049-10. Epub 2010 Jul 7.

Abstract

A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Spleen / immunology
  • Survival Analysis
  • T-Lymphocytes / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology

Substances

  • Viral Vaccines