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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/06/1969/07 $2.00
Volume 185, Number 11, June 2, 1997 1969-1975

T Cell Receptor-gamma /delta Cells Protect Mice from Herpes Simplex Virus Type 1-induced Lethal Encephalitis

By Roger Sciammas,* P. Kodukula,Dagger Q. Tang,Dagger R.L. Hendricks,Dagger and J.A. Bluestone*

From the * Ben May Institute for Cancer Research, Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637; and the Dagger  Department of Ophthalmology Visual Sciences and Department of Pathology, University of Illinois at Chicago, Chicago, Illinois 60612

Increased numbers of T cell receptor (TCR)-gamma /delta cells have been observed in animal models of influenza and sendai virus infections, as well as in patients infected with human immunodeficiency virus and herpes simplex virus type 1 (HSV-1). However, a direct role for TCR-gamma /delta cells in protective immunity for pathogenic viral infection has not been demonstrated. To define the role of TCR-gamma /delta cells in anti-HSV-1 immunity, TCR-alpha -/- mice treated with anti- TCR-gamma /delta monoclonal antibodies or TCR-gamma /delta × TCR-alpha /beta double-deficient mice were infected with HSV-1 by footpad or ocular routes of infection. In both models of HSV-1 infection, TCR-gamma /delta cells limited severe HSV-1-induced epithelial lesions and greatly reduced mortality by preventing the development of lethal viral encephalitis. The observed protection resulted from TCR-gamma /delta cell-mediated arrest of both viral replication and neurovirulence. The demonstration that TCR-gamma /delta cells play an important protective role in murine HSV-1 infections supports their potential contribution to the immune responses in human HSV-1 infection. Thus, this study demonstrates that TCR-gamma /delta cells may play an important regulatory role in human HSV-1 infections.


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