Dermal IL-17-producing gamma delta T cells establish long-lived memory in the skin

Conventional alpha beta T cells have the ability to form a long-lasting resident memory T-cell (T sub(RM)) population in nonlymphoid tissues after encountering foreign antigen. Conversely, the concept of 'innate memory', where the ability of nonadaptive branches of the immune system to deliver a rapid, strengthened immune response upon reinfection or rechallenge, is just emerging. Using the alpha beta T-cell-independent Aldara psoriasis mouse model in combination with genetic fate-mapping and reporter systems, we identified a subset of gamma delta T cells in mice that is capable of establishing a long-lived memory population in the skin. IL-17A/F-producing V gamma 4 super(+)V delta 4 super(+) T cells populate and persist in the dermis for long periods of time after initial stimulation with Aldara. Experienced V gamma 4 super(+)V delta 4 super(+) cells show enhanced effector functions and mediate an exacerbated secondary inflammatory response. In addition to identifying a unique feature of gamma delta T cells during inflammation, our results have direct relevance to the human disease as this quasi-innate memory provides a mechanistic insight into relapses and chronification of psoriasis.