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

doi:10.1084/jem.185.11.1969

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© The Rockefeller University Press, 0022-1007/1997/6/1969/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 11, June 2, 1997 1969-1975

Article

T Cell Receptor– ${gamma}$ / ${delta}$ Cells Protect Mice from Herpes Simplex Virus Type 1–induced Lethal Encephalitis

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)- ${gamma}$ / ${delta}$ cells have beenobserved in animal models of influenza and sendai virus infections,as well as in patients infected with human immunodeficiencyvirus and herpes simplex virus type 1 (HSV-1). However, a directrole for TCR- ${gamma}$ / ${delta}$ cells in protective immunity for pathogenicviral infection has not been demonstrated. To define the roleof TCR- ${gamma}$ / ${delta}$ cells in anti–HSV-1 immunity, TCR- ${alpha}$ ^–/–mice treated with anti– TCR- ${gamma}$ / ${delta}$ monoclonal antibodies orTCR- ${gamma}$ / ${delta}$ x TCR- ${alpha}$ /β double-deficient mice were infected withHSV-1 by footpad or ocular routes of infection. In both modelsof HSV-1 infection, TCR- ${gamma}$ / ${delta}$ cells limited severe HSV-1–inducedepithelial lesions and greatly reduced mortality by preventingthe development of lethal viral encephalitis. The observed protection resulted from TCR- ${gamma}$ / ${delta}$ cell–mediated arrest of both viralreplication and neurovirulence. The demonstration that TCR- ${gamma}$ / ${delta}$ cells play an important protective role in murine HSV-1 infectionssupports their potential contribution to the immune responsesin human HSV-1 infection. Thus, this study demonstrates thatTCR- ${gamma}$ / ${delta}$ cells may play an important regulatory role in humanHSV-1 infections.

Address correspondence to Jeffrey A. Bluestone, Ben May Institutefor Cancer Research, University of Chicago, MC 1089, 5841 S.Maryland Ave., Chicago, IL 60637.

R. Sciammas is supported by a National Institutes of Health/NationalInstitute of Allergy and Infectious Diseases interdisciplinarytraining program in immunology No. 5T32A107090, J. Bluestoneis supported by a grant from the National Institutes of HealthNo. RO1 AI26847, and P. Kodukula, Q. Tang, and R.L. Hendricksare supported by grants from the National Institutes of HealthNo. EY10359, EY05945, and EY01792.

R. Sciammas and P. Kodukula contributed equally to this work.

¹Abbreviations used in this paper: HSK, herpetic stromal keratitis;rh, recombinant human.

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