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-/ Cells Protect Mice from Herpes Simplex Virus Type 1-induced Lethal Encephalitis

By Roger Sciammas,^* P. Kodukula, Q. Tang, R.L. Hendricks, 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  Department of Ophthalmology Visual Sciences and Department of Pathology, University of Illinois at Chicago, Chicago, Illinois 60612

Increased numbers of T cell receptor (TCR)-/ 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-/ cells in protective immunity for pathogenic viral infection has not been demonstrated. To define the role of TCR-/ cells in anti-HSV-1 immunity, TCR-^/ mice treated with anti- TCR-/ monoclonal antibodies or TCR-/ × TCR-/ double-deficient mice were infected with HSV-1 by footpad or ocular routes of infection. In both models of HSV-1 infection, TCR-/ 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-/ cell-mediated arrest of both viral replication and neurovirulence. The demonstration that TCR-/ 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-/ cells may play an important regulatory role in human HSV-1 infections.

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