Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children.
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.
Zhang
Qibo
Q
Department of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, United Kingdom. q.zhang@bristol.ac.uk
Bagrade
Linda
L
Bernatoniene
Jolanta
J
Clarke
Ed
E
Paton
James C
JC
Mitchell
Tim J
TJ
Nunez
Desmond A
DA
Finn
Adam
A
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
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