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Infection and Immunity, January 2001, p. 271-280, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.271-280.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL+ T and B Cells during Murine Schistosoma mansoni Infection

Steven K. Lundy, Stephen P. Lerman, and Dov L. Boros*

Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201

Received 20 June 2000/Returned for modification 4 August 2000/Accepted 23 October 2000

Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated by the activity of CD4+ Th lymphocytes and their cytokines. Regulation of the inflammatory Th cell response during infection is still insufficiently understood. The hypothesis of this study was that activation-induced cell death (AICD) of CD4+ T cells is involved in the immune inflammatory response. This study investigated the dynamics of splenic and granuloma CD4+ Th cell apoptosis and Fas ligand (FasL) expression during the acute and chronic stages of murine schistosomal infection. Enhanced apoptosis of freshly isolated CD4+ Th lymphocytes commenced after egg deposition and persisted during the peak and modulated phases of granuloma formation. After oviposition, CD4+, CD8+, and CD19+ splenocytes and granuloma cells expressed elevated levels of FasL but FasL expression declined during the downmodulated stage of infection. In culture, SEA induced splenic and granuloma CD4+ T-cell apoptosis and stimulated expression of FasL on splenic but not granuloma CD4+ T cells, CD8+ T cells, and CD19+ B cells. SEA-stimulated splenocytes and granuloma cells preferentially lysed a Fas-transfected target cell line. Depletion of B cells from SEA-stimulated splenic cultures decreased CD4+ T cell apoptosis. Coculture of purified splenic B cells with CD4+ T cells and adoptive transfer of purified B cells indicated that antigen-stimulated B cells can kill CD4+ Th cells. However, CD4+ T cells were the dominant mediators of apoptosis in the granuloma. This study indicates that AICD is involved in the apoptosis of CD4+ T cells during schistosomal infection.

* Corresponding author. Mailing address: Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201. Phone: (313) 577-1493. Fax: (313) 577-1155. E-mail: dboros{at}med.wayne.edu.

Infection and Immunity, January 2001, p. 271-280, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.271-280.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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