Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte-targeted overexpression of IL-15

Karin Loser, Annette Mehling, Jenny Apelt, Sonja Ständer, Pietro G. Andres, Hans Christian Reinecker, Bodo R. Eing, Boris V. Skryabin, Georg Varga, Thomas Schwarz, Stefan Beissert

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

IL-15 is involved in lymphocyte homeostasis. To investigate the role of IL-15 in the skin in vivo, mice were generated that overexpress IL-15 in keratinocytes, resulting in increased IL-15 protein levels in the skin but not elevated IL-15 serum concentrations. Keratin 14 (K14)-IL-15 transgenic (tg) mice showed increased contact hypersensitivity (CHS) responses. Transfer of primed wild-type (wt) and tg T cells into naive wt or tg recipients indicated that skin-derived IL-15 enhanced the induction but not the elicitation phase of CHS. Tg mice could be sensitized even by suboptimal hapten concentrations. Accordingly, Langerhans cells (LC) from tg skin were identified as potent allostimulators, suggesting the involvement of IL-15-stimulated LC in the induction of adaptive immunity. Overexpression of IL-15 also strengthened innate immunity since tg mice infected with human HSV type I developed significantly smaller HSV skin lesions. In addition, tg mice resisted re-infection with HSV more effectively than wt mice did, which was associated with an elevated anti-HSV Ab production. Accordingly, injection of serum from re-infected tg mice protected naive recipients significantly from epicutaneous HSV infection, indicating that anti-HSV Ab produced by tg mice play an important role in resistance in vivo. Together, our results show that overexpression of IL-15 in the epidermis enhances both innate and adaptive cutaneous immunity.

Original languageEnglish (US)
Pages (from-to)2022-2031
Number of pages10
JournalEuropean Journal of Immunology
Volume34
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • HSV infection
  • IL-15
  • T lymphocytes
  • Transgenic mice
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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