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Journal of Virology, November 2008, p. 10820-10831, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00365-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response{triangledown}

Subhadra Nandakumar,1 Stacie N. Woolard,1 Dorothy Yuan,2 Barry T. Rouse,3 and Uday Kumaraguru1*

Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614,1 Dept. of Pathology, UT South Western Medical Center, Dallas, Texas,2 Dept. of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 379963

Received 19 February 2008/ Accepted 14 August 2008

Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8+ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8+ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

* Corresponding author. Mailing address: Department of Microbiology, Box 70579, Quillen College of Medicine, ETSU, Johnson City, TN 37614. Phone: (423) 439-6227. Fax: (423) 439-8044. E-mail: kumaragu{at}etsu.edu

{triangledown} Published ahead of print on 20 August 2008.

Journal of Virology, November 2008, p. 10820-10831, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00365-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Morandi, B., Mortara, L., Carrega, P., Cantoni, C., Costa, G., Accolla, R. S., Mingari, M. C., Ferrini, S., Moretta, L., Ferlazzo, G. (2009). NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs. Int Immunol 21: 599-606 [Abstract] [Full Text]  


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