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

D. Kruijsen, M.J. Bakkers, N.O.P. van Uden, M.C. Viveen, T.C. van der Sluis, J.L.L. Kimpen, J.H.W. Leusen, F.E.J. Coenjaerts, G.M. van Bleek

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)6489-6498
Number of pages10
JournalJournal of Immunology
Volume185
Issue number11
DOIs
Publication statusPublished - 1 Dec 2010

Keywords

  • Adaptive Immunity
  • Animals
  • Antibodies, Viral
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Dendritic Cells
  • Epitopes, T-Lymphocyte
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NIH 3T3 Cells
  • Respiratory Syncytial Virus Infections
  • Respiratory Syncytial Viruses
  • Journal Article
  • Research Support, Non-U.S. Gov't

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