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Infection and Immunity, December 1999, p. 6394-6402, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cytolethal Distending Toxin of Haemophilus ducreyi Induces Apoptotic Death of Jurkat T Cells

Valentina Gelfanova,1 Eric J. Hansen,2 and Stanley M. Spinola1,3,4,*

Departments of Medicine,1 Microbiology and Immunology,3 and Pathology and Laboratory Medicine,4 Indiana University, Indianapolis, Indiana 46202, and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-90482

Received 1 June 1999/Returned for modification 28 July 1999/Accepted 10 September 1999

The immune response to Haemophilus ducreyi is mediated in part by T cells infiltrating the site of infection. In this study, we show that H. ducreyi antigen preparations inhibited the proliferation of peripheral blood mononuclear cells and primary human T-cell lines. H. ducreyi also inhibited Jurkat T-cell proliferation and induced apoptosis of Jurkat T cells, confirmed through the detection of DNA degradation and membrane unpacking. The cytotoxic product(s) was present in cell-free culture supernatant and whole-cell preparations of H. ducreyi and was heat labile. H. ducreyi produces two known heat-labile toxins, a hemolysin and a cytolethal distending toxin (CDT). Whole cells and supernatants prepared from a hemolysin-deficient mutant had the same inhibitory and apoptotic effects on Jurkat T cells as did its isogenic parent. Preparations made from an H. ducreyi cdtC mutant were less toxic and induced less apoptosis than the parent. The toxic activity of the cdtC mutant was restored by complementation in trans. CdtC-neutralizing antibodies also inhibited H. ducreyi-induced toxicity and apoptosis. The data suggest that CDT may interfere with T-cell responses to H. ducreyi by induction of apoptosis.

* Corresponding author. Mailing address: Department of Medicine, Emerson Hall, Rm. 435, 545 Barnhill Dr., Indianapolis, IN 46202. Phone: (317) 274-1427. Fax: (317) 274-1587. E-mail: sspinola{at}iupui.edu.

Infection and Immunity, December 1999, p. 6394-6402, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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