Blood 107(10): 3925-3932

Activated CD4<sup>+</sup>CD25<sup>+</sup> T cells selectively kill B lymphocytes

From the Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD.

Reprints: Ethan M. Shevach, Bldg 10, Rm 11N315, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; e-mail: vog.hin.diain@hcavehse.

Received 2005 Nov 14; Accepted 2005 Dec 30.

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.}

Abstract

Acknowledgments

We thank Drs Pierce Henkart and Itzhak Mendel for helpful discussions and Ms Sarah Tanksley for cell sorting.

Acknowledgments

Notes

Prepublished online as Blood First Edition Paper, January 17, 2006; DOI 10.1182/blood-2005-11-4502.

An Inside Blood analysis of this article appears at the front of this issue.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

Notes

Prepublished online as Blood First Edition Paper, January 17, 2006; DOI 10.1182/blood-2005-11-4502.An Inside Blood analysis of this article appears at the front of this issue.

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