Serum antibodies critically affect virus-specific CD4+/CD8+ T cell balance during respiratory syncytial virus infections

J Immunol. 2010 Dec 1;185(11):6489-98. doi: 10.4049/jimmunol.1002645. Epub 2010 Oct 22.

Abstract

Following infection with respiratory syncytial virus (RSV), reinfection in healthy individuals is common and presumably due to ineffective memory T cell responses. In peripheral blood of healthy adults, a higher CD4(+)/CD8(+) memory T cell ratio was observed compared with the ratio of virus-specific effector CD4(+)/CD8(+) T cells that we had found in earlier work during primary RSV infections. In mice, we show that an enhanced ratio of RSV-specific neutralizing to nonneutralizing Abs profoundly enhanced the CD4(+) T cell response during RSV infection. Moreover, FcγRs and complement factor C1q contributed to this Ab-mediated enhancement. Therefore, the increase in CD4(+) memory T cell response likely occurs through enhanced endosomal Ag processing dependent on FcγRs. The resulting shift in memory T cell response was likely amplified by suppressed T cell proliferation caused by RSV infection of APCs, a route important for Ag presentation via MHC class I molecules leading to CD8(+) T cell activation. Decreasing memory CD8(+) T cell numbers could explain the inadequate immunity during repeated RSV infections. Understanding this interplay of Ab-mediated CD4(+) memory T cell response enhancement and infection mediated CD8(+) memory T cell suppression is likely critical for development of effective RSV vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Viral / blood*
  • Antigen Presentation / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / virology
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NIH 3T3 Cells
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / immunology*

Substances

  • Antibodies, Viral
  • Epitopes, T-Lymphocyte