Lethal effects of Actinobacillus actinomycetemcomitans leukotoxin on human T lymphocytes

Abstract

The majority of strains of Actinobacillus actinomycetemcomitans isolated from patients with periodontal diseases secrete a leukotoxin that destroys human myeloid cells within minutes but has no effect on viability of peripheral blood lymphocytes in culture for 1.5 h. However, since this organism persists in the gingival crevice and thus may continuously release toxin over extended periods of time, we assessed the viability of T cells cultured with leukotoxin (0 to 250 ng/ml) for up to 2 days. Although the total numbers of cells recovered from cultures with or without leukotoxin were equivalent, leukotoxin killed up to 70% of the T cells in a time- and concentration-dependent manner. Cell death was associated with uptake of propidium iodide, release of 51Cr from the cytoplasm, and morphological evidence of damage to the plasma membrane and apoptosis. Leukotoxin also induced increased cleavage of chromosomal DNA into nucleosome-sized fragments, suggesting activation of an endogenous nuclease in the T cells. These data suggest that leukotoxin kills T cells by pathways resembling necrosis and programmed cell death. Leukotoxin-induced lymphotoxicity may represent a critical mechanism by which A. actinomycetemcomitans suppresses the host local immune response and contributes to the pathogenesis of diseases involving this microorganism.