Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte-targeted overexpression of IL-15.
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.
Loser
Karin
K
Department of Dermatology, University of Münster, Münster, Germany.
Mehling
Annette
A
Apelt
Jenny
J
Ständer
Sonja
S
Andres
Pietro G
PG
Reinecker
Hans-Christian
HC
Eing
Bodo R
BR
Skryabin
Boris V
BV
Varga
Georg
G
Schwarz
Thomas
T
Beissert
Stefan
S
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003877:Dermatitis, Contact / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006561:Herpes Simplex / Q000097:blood / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D019409:Interleukin-15 / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000485:Allergens; D019409:Interleukin-15