Cytolethal distending toxin of Haemophilus ducreyi induces apoptotic deathof Jurkat T cells

The immune response to Haemophilus ducreyi is mediated in part by T cells i nfiltrating the site of infection. Zn this study, we show that H. ducreyi a ntigen preparations inhibited the proliferation of peripheral blood mononuc lear cells and primary human T-cell lines. H. ducreyi also inhibited Jurkat T-cell proliferation and induced apoptosis of Jurkat T cells, confirmed th rough the detection of DNA degradation and membrane unpacking, The cytotoxi c product(s) was present in cell-free culture supernatant and whole-cell pr eparations of H. ducreyi and was heat labile. H. ducreyi produces two known heat-labile toxins, a hemolysin and a cytolethal distending toxin (CDT). W hole cells and supernatants prepared from a hemolysin-deficient mutant had the same inhibitory and apoptotic effects on Jurkat T cells as did its isog enic parent. preparations made from an H. ducreyi cdtC mutant,were less tox ic and induced less apoptosis than the parent. The toxic activity of the cd tC mutant was restored by complementation in trans, CdtC-neutralizing antib odies also inhibited H. ducreyi-induced toxicity: and apoptosis, The data s uggest that CDT may interfere with T-cell responses to H. ducreyi by induct ion of apoptosis.