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J. Biol. Chem., Vol. 277, Issue 37, 34329-34335, September 13, 2002

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Skin-stage Schistosomula of Schistosoma mansoni Produce an Apoptosis-inducing Factor That Can Cause Apoptosis of T Cells^*

Lin Chen, Kakuturu V. N. Rao^§, Yi-Xun He, and Kalyanasundaram Ramaswamy^¶

From the  Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, Illinois 61107 and the ^§ Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208

Skin-stage schistosomula of Schistosoma mansoni were found to secrete molecules that are pro-apoptotic for skin T lymphocytes as measured by annexin V staining, caspase-3 activity, caspase-8 activities, and DNA fragmentation. Caspase-8 activities in lymphocytes peaked ~8 h and caspase-3 activity peaked ~16 h after exposure to the parasite secretions. Subset analysis showed that mainly CD4⁺ and CD8⁺ cells (but not B cells) were susceptible to the parasite-induced pro-apoptotic effect. In situ staining confirmed the presence of apoptotic T cells around challenge parasites in the skin of naive or immunized animals. Analysis of T cells to identify the potential molecular pathway of the parasite-induced apoptosis showed increases in the expression of Fas, FasL, and the Fas-associated death domain. Blocking of FasL with a fusion protein reversed the parasite-induced apoptosis, suggesting a role for the Fas/FasL-mediated pathway in the parasite-induced T cell apoptosis. Subsequent analyses of the secretions of skin-stage schistosomula identified the pro-apoptotic activity as being associated with a protein of ~23 kDa. This protein was termed S. mansoni-derived apoptosis-inducing factor.

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