Overexpression of interleukin-15 compromises CD4-dependent adaptive immune responses against herpes simplex virus 2

J Virol. 2009 Jan;83(2):918-26. doi: 10.1128/JVI.01282-08. Epub 2008 Nov 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Genitalia / cytology
  • Genitalia / immunology
  • Herpes Genitalis / immunology*
  • Herpesvirus 2, Human / immunology*
  • Immunization, Passive
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Survival Analysis


  • Interleukin-15