The Immune Regulatory Function of Lymphoproliferative Double Negative T Cells In Vitro and In Vivo

doi:10.1084/jem.20020029

Published 15 July 2002. doi:10.1084/jem.20020029

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© Rockefeller University Press, 0022-1007/2002/7/261/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 2, July 15, 2002 261-267

Brief Definitive Report

The Immune Regulatory Function of Lymphoproliferative Double Negative T Cells In Vitro and In Vivo

Megan S. Ford¹, Kevin J. Young¹, Zhuxu Zhang¹, Pamela S. Ohashi² and Li Zhang¹

¹ Department of Laboratory Medicine and Pathobiology and Department of Immunology, University of Toronto, Multi Organ Transplantation Program, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada
² Department of Medical Biophysics and Immunology, University of Toronto, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada

Address correspondence to Li Zhang, Toronto General Hospital Research Institute, Department of Laboratory Medicine and Pathobiology, CCRW 2-809, 101 College Street, Toronto, Ontario M5G 2C4, Canada. Phone: 416-340-4915; Fax: 416-597-9749; E-mail: lzhang{at}transplantunit.org

Lymphoproliferative (lpr) mice, which lack functional Fas receptorexpression and develop autoimmune lymphoproliferative disease,have an accumulation of T cell receptor- ${alpha}$ ß⁺CD4^-CD8^-(double negative T cells [DNTC]) in the periphery. The functionof the accumulating DNTC is not clear. In this study we demonstratethat B6/lpr DNTC can dose dependently kill syngeneic CD8⁺ andCD4⁺ T cells from wild-type B6 mice through Fas/Fas ligand interactionsin vitro. We also demonstrate that B6/lpr DNTC that are activatedand expand in vivo are able to specifically down-regulate allogeneicimmune responses mediated by syngeneic Fas⁺CD4⁺ and CD8⁺ T cellsin vivo. B6/lpr DNTC that have been preactivated in vivo byinfusion of either class I– (bm1) or class II– (bm12)mismatched allogeneic lymphocytes are able to specifically enhancethe survival of bm1 or bm12, but not third-party skin allograftswhen adoptively transferred into naive B6^+/+ mice. These findingsclearly demonstrate that B6/lpr DNTC have a potent immune regulatoryfunction in vitro and in vivo. They also provide new insightsinto the mechanisms involved in the development of autoimmunedisease in lpr mice.

Key Words: autoimmune • transplantation • immune tolerance • suppressor T lymphocytes • Fas ligand

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