Transgenic Mice with Exaggerated Contact Hypersensitivity Responses

Emory University
posted on 07/07/2009

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Applications

• Testing of therapeutics that seek to inhibit consequences of T cell-mediated immune responses.
• Identification of chemicals with weak contact sensitizing activity.

Technical Summary

The keratinocytes of the mouse model constitutively express both the costimulatory molecule B7-1 and the human class II transactivator (CIITA) proten. B7-1 provides an important second signal for T cell activation and CIITA induces the expression of class II MHC molecules involved in antigen presentation to T cells at high levels. As a result of keratinocyte B7-1 and class II MHC expression, the mice are predisposed to develop substantially increased contact hypersensitivity responses after sensitization to contact sensitizing agents.

This transgenic mouse line exhibits strongly enhanced skin immune response to contact sensitizing chemicals without an appreciable change in the basal level of cutaneous inflammation. In contrast, other transgenic mouse models showing increased skin inflammation all have significant baseline changes in their cutaneous biology subsequent to overespression of cytokines or growth factors.