Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children

J Infect Dis. 2007 Apr 15;195(8):1194-202. doi: 10.1086/512617. Epub 2007 Mar 6.

Abstract

Background: Recent studies in mice have suggested that T cell immunity may be protective against pneumococcal infection.

Methods: CD4 T cell proliferative responses to the pneumococcal proteins pneumolysin (Ply), Ply toxoid (F433), and choline-binding protein A were investigated in peripheral blood mononuclear cells (PBMCs) and adenoidal mononuclear cells (MNCs) obtained from children undergoing adenoidectomy.

Results: Ply and F433 induce significant proliferation of CD4 T cells in both PBMCs and adenoidal MNCs, and both memory and naive phenotypes of CD4 T cells proliferated after stimulation. In PBMCs, CD4 T cell proliferation induced by Ply and F433, which was associated with increased production of interferon (IFN)- gamma and tumor necrosis factor (TNF)- alpha , was significantly lower in children who were culture positive for pneumococcus than in those who were culture negative for pneumococcus (P<.05). Between groups, no such difference was observed in adenoidal MNC CD4 T cell proliferation, which was associated with production of IFN- gamma and interleukin (IL)-10. The CD4 T cell proliferation induced by Ply and F433 was inhibited by antibodies to Toll-like receptor 4.

Conclusion: These data suggest that Ply induces CD4 T cell proliferative responses with production of IFN- gamma and TNF- alpha in PBMCs or of IFN- gamma and IL-10 in adenoidal MNCs, which may be important in modulating pneumococcal carriage in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / metabolism
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Carrier State / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Male
  • Nasopharynx / microbiology*
  • Pneumococcal Infections / immunology*
  • Streptococcus pneumoniae / isolation & purification*
  • Streptolysins / immunology*
  • Time Factors
  • Toll-Like Receptors / immunology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • SpsA protein, Streptococcus pneumoniae
  • Streptolysins
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • plY protein, Streptococcus pneumoniae
  • Interferon-gamma