Activated CD4+CD25+ T cells selectively kill B lymphocytes |
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Authors: | Zhao Dong-Mei Thornton Angela M DiPaolo Richard J Shevach Ethan M |
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Institution: | Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 10, Rm 11N315, Bethesda, MD 20892, USA. |
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Abstract: | The suppressive capacity of naturally occurring mouse CD4+CD25+ T cells on T-cell activation has been well documented. The present study is focused on the interaction of CD4+CD25+ T cells and B cells. By coculturing preactivated CD4+CD25+ T cells with B cells in the presence of polyclonal B-cell activators, we found that B-cell proliferation was significantly suppressed. The suppression of B-cell proliferation was due to increased cell death caused by the CD4+CD25+ T cells in a cell-contact-dependent manner. The induction of B-cell death is not mediated by Fas-Fas ligand pathway, but surprisingly, depends on the up-regulation of perforin and granzymes in the CD4+CD25+ T cells. Furthermore, activated CD4+CD25+ T cells preferentially killed antigen-presenting but not bystander B cells. Our results demonstrate that CD4+CD25+ T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+ T cells can be explained, at least in part, by the direct regulation of B-cell function. |
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