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Infection and Immunity, January 2001, p. 271-280, Vol. 69, No. 1
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.
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
*
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.
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