title: Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, United Kingdom. q.zhang@bristol.ac.uk
authors.forename: Qibo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Linda
authors.initials: L
authors.lastname: Bagrade
authors.forename: Jolanta
authors.initials: J
authors.lastname: Bernatoniene
authors.forename: Ed
authors.initials: E
authors.lastname: Clarke
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Nunez
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002353:Carrier State / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D013301:Streptolysins / Q000276:immunology*; D013997:Time Factors; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D013301:Streptolysins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C032290:plY protein, Streptococcus pneumoniae; D007371:Interferon-gamma