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Journal of Virology, May 2009, p. 5256-5268, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01997-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CD4⁺ T Cells Are Required for the Priming of CD8⁺ T Cells following Infection with Herpes Simplex Virus Type 1 ^,

Naveen K. Rajasagi,^1,2, Sadik H. Kassim,^1,2, Christina M. Kollias,² Xiangyi Zhao,² Robert Chervenak,¹ and Stephen R. Jennings^2*

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130,¹ Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129²

Received 22 September 2008/ Accepted 1 March 2009

The role of CD4⁺ helper T cells in modulating the acquired immune response to herpes simplex virus type 1 (HSV-1) remains ill defined; in particular, it is unclear whether CD4⁺ T cells are needed for the generation of the protective HSV-1-specific CD8⁺-T-cell response. This study examined the contribution of CD4⁺ T cells in the generation of the primary CD8⁺-T-cell responses following acute infection with HSV-1. The results demonstrate that the CD8⁺-T-cell response generated in the draining lymph nodes of CD4⁺-T-cell-depleted C57BL/6 mice and B6-MHC-II^–/– mice is quantitatively and qualitatively distinct from the CD8⁺ T cells generated in normal C57BL/6 mice. Phenotypic analyses show that virus-specific CD8⁺ T cells express comparable levels of the activation marker CD44 in mice lacking CD4⁺ T cells and normal mice. In contrast, CD8⁺ T cells generated in the absence of CD4⁺ T cells express the interleukin 2 receptor -chain (CD25) at lower levels. Importantly, the CD8⁺ T cells in the CD4⁺-T-cell-deficient environment are functionally active with respect to the expression of cytolytic activity in vivo but exhibit a diminished capacity to produce gamma interferon and tumor necrosis factor alpha. Furthermore, the primary expansion of HSV-1-specific CD8⁺ T cells is diminished in the absence of CD4⁺-T-cell help. These results suggest that CD4⁺-T-cell help is essential for the generation of fully functional CD8⁺ T cells during the primary response to HSV-1 infection.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology (Room 18107), Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19102. Phone: (215) 762-3719. Fax: (215) 762-1955. E-mail: stephen.jennings{at}drexelmed.edu

Published ahead of print on 11 March 2009.

We dedicate this paper to our late colleague, Patrick Mitchell Smith (1956 to 2007).

Present address: Department of Microbiology, University of Tennessee, Knoxville, TN 37996.

Present address: Gene Therapy Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

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Journal of Virology, May 2009, p. 5256-5268, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01997-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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