A phenotypic analysis of involucrin-mOVA mice following adoptive transfer of OVA-specific CD8+ T cells

ABSTRACT

To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 (K5) and keratin 14 (K14), were employed in combination with adoptive transfer of OT-I T cells that recognize an OVA-derived peptide. However, these strains showed body weight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. Here we generated a mouse strain expressing mOVA under the control of human involucrin (Ivl) promoter (Ivl-mOVA mice). In contrast to previous strains, Ivl-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant body weight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite remaining OT-I T cells in the skin. Our Ivl-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity.