Role of alpha beta T cells and gamma delta T cells in protective immunity to Actinobacillus actinomycetemcomitans in mutant mice by targeted gene disruption.

Abstract

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.