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Adaptive immune responses fail to provide protection against genital HSV-2 infection in the absence of IL-15.

Abstract
IL-15 plays a crucial role in innate defense against viral infections. The role of IL-15 in the generation and function of adaptive immunity, following mucosal immunization, against genital HSV-2 has not been studied. Here, we report that immunized IL-15(-/-) mice were able to generate antibody and T cell-mediated immune responses against HSV-2, comparable to those seen in immunized B6 mice. However, immunized IL-15(-/-) mice were not protected against subsequent HSV-2 challenge, compared to B6 immunized mice, even with a ten times lower challenge dose. We then examined if the adaptive immune responses generated in the absence of IL-15 could provide protection against HSV-2 in an IL-15-positive environment. Adoptive transfer of lymphocytes from immunized IL-15(-/-) to naive mice were able to provide protection against HSV-2 challenge similar to protection with immunized cells from control mice. This suggests that the adaptive immune responses raised in the absence of IL-15 are functional in vivo. Reconstitution of the innate components, particularly IL-15, NK cells and NK cell-derived IFN-gamma, in immunized IL-15(-/-) mice restored their protective adaptive immunity against subsequent genital HSV-2 challenge. Our results clearly suggest that innate antiviral activity of IL-15 is necessary for protective adaptive immunity against genital HSV-2 infection.
AuthorsNavkiran Gill, Ali A Ashkar
JournalEuropean journal of immunology (Eur J Immunol) Vol. 37 Issue 9 Pg. 2529-38 (Sep 2007) ISSN: 0014-2980 [Print] Germany
PMID17668897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Interleukin-15
  • Recombinant Proteins
Topics
  • Adaptation, Biological (immunology)
  • Animals
  • Antiviral Agents (pharmacology)
  • Female
  • Herpes Genitalis (immunology, pathology, virology)
  • Herpesvirus 2, Human (drug effects, immunology)
  • Immunization
  • Interleukin-15 (deficiency, genetics, metabolism, pharmacology)
  • Killer Cells, Natural (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane (immunology)
  • Recombinant Proteins (pharmacology)
  • Survival Rate

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