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Journal of Virology, January 2009, p. 918-926, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01282-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Overexpression of Interleukin-15 Compromises CD4-Dependent Adaptive Immune Responses against Herpes Simplex Virus 2{triangledown} ,{dagger}

Navkiran Gill and Ali A. Ashkar*

Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada

Received 19 June 2008/ Accepted 3 November 2008

Interleukin-15 (IL-15) is necessary for the development and function of NK/NKT cells and the maintenance of naive and memory CD8+ T cells. In the absence of IL-15, protective innate immunity is not available; however, a functional adaptive immune response against vaginal herpes simplex virus 2 (HSV-2) is generated. Mice overexpressing IL-15 (IL-15tg mice) have higher numbers of NK cells, greater NK-derived gamma interferon, and more CD8+ T cells. Here we examined the consequences of IL-15 overexpression for innate and adaptive immunity against genital HSV-2. Surprisingly, IL-15tg mice immunized against HSV-2 were not protected against genital HSV-2 challenge compared to control immunized mice. IL-15tg mice had a higher frequency of NK cells in the genital mucosa than control mice. However, immunized IL-15tg mice had significantly lower numbers of HSV-2-specific CD4+ T cells than B6 mice. We then confirmed that CD4+ T cells, but not CD8+ T cells, are essential for protection against intravaginal HSV-2 challenge. Since we observed less protection in immunized IL-15tg mice, we then examined if the adaptive immune responses generated in an environment with overexpression of IL-15 could provide protection against HSV-2 in an environment with normal levels of IL-15 expression. We adoptively transferred immunized cells from IL-15tg and B6 mice into naive RAG-1–/– mice and found that the cells from immunized IL-15tg mice were able to provide protection in this IL-15-normal environment. Our data suggest that overexpression of IL-15 results in a reduced CD4+ T cell-mediated adaptive immune response against genital HSV-2.

* Corresponding author. Mailing address: Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140, ext. 22311. Fax: (905) 522-6750. E-mail: ashkara{at}mcmaster.ca

{triangledown} Published ahead of print on 12 November 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, January 2009, p. 918-926, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01282-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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