Role of alpha beta T cells and gamma delta T cells in protective immunity to Actinobacillus actinomycetemcomitans in mutant mice by targeted gene disruption.
The relative roles of alpha beta or gamma delta T cells in protection against Actinobacillus actinomycetemcomitans were analysed by using mutant mice deficient in alpha beta or gamma delta T cell receptor (TCR). The dose of A. actinomycetemcomitans producing lethality for the TCR-alpha deficient mice was 25% of that for control C57BL/6 mice, while that of TCR-delta deficient mice was similar to that of C57BL/6 mice. Reverse transcription (RT)-PCR revealed that gamma delta T cells from the A. actinomycetemcomitans-infected alpha beta TCR deficient mice expressed significant levels of interferon (IFN)-gamma, interleukin (IL)-5 and IL-6 mRNA, whereas alpha beta T cells from A. actinomycetemcomitans-infected gamma delta TCR deficient mice exhibited significant levels of IFN-gamma and IL-2 mRNA. Delayed-type hypersensitivity (DTH) reactions against heat shock protein (HSP) 60 were prominently observed in A. actinomycetemcomitans-infected TCR-delta mutant and C57BL/6 mice, but were absent in TCR-alpha mutant mice, suggesting that the DTH response is exclusively dependent on HSP60-specific alpha beta T cells producing IFN-gamma and IL-2 mRNA. It was found that all the mice used exhibited similar levels of serum IgG and IgM responses against A. actinomycetemcomitans-specific antigens (whole cells and HSP60), suggesting that alpha beta as well as gamma delta T cells participate in the serum immune responses. In addition, the humoral antibody responses displayed in the TCR-alpha deficient mice implies resistance to A. actinomycetemcomitans infection. Thus, the resistance to A. actinomycetemcomitans infection may be ascribed mainly to alpha beta T cells, while gamma delta T cells can partially compensate for the alpha beta T cell defect.
Takahashi
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Department of Oral Microbiology, Osaka University, Faculty of Dentistry, Japan.
Nakagawa
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Xu
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Hamada
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S
D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics; D015848:Interleukin-5 / Q000032:analysis / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma