Fiorenza, S.Kenna, T.Comerford, I.McColl, S.Steptoe, R.Leggatt, G.Frazer, I.2013-01-302013-01-302012Journal of Immunology, 2012; 189(12):5622-56310022-17671550-6606http://hdl.handle.net/2440/75131Adoptive T cell therapy uses the specificity of the adaptive immune system to target cancer and virally infected cells. Yet the mechanism and means by which to enhance T cell function are incompletely described, especially in the skin. In this study, we use a murine model of immunotherapy to optimize cell-mediated immunity in the skin. We show that in vitro–derived central but not effector memory-like T cells bring about rapid regression of skin-expressing cognate Ag as a transgene in keratinocytes. Local inflammation induced by the TLR7 receptor agonist imiquimod subtly yet reproducibly decreases time to skin graft rejection elicited by central but not effector memory T cells in an immunodeficient mouse model. Local CCL4, a chemokine liberated by TLR7 agonism, similarly enhances central memory T cell function. In this model, IL-2 facilitates the development in vivo of effector function from central memory but not effector memory T cells. In a model of T cell tolerogenesis, we further show that adoptively transferred central but not effector memory T cells can give rise to successful cutaneous immunity, which is dependent on a local inflammatory cue in the target tissue at the time of adoptive T cell transfer. Thus, adoptive T cell therapy efficacy can be enhanced if CD8+ T cells with a central memory T cell phenotype are transferred, and IL-2 is present with contemporaneous local inflammation.enCopyright © 2012 by The American Association of Immunologists, IncEpidermisT-Lymphocyte SubsetsCells, CulturedSkinAnimalsMice, Inbred C57BLMice, TransgenicMice, KnockoutMiceInflammationAdoptive TransferSkin TransplantationCell CommunicationImmune ToleranceImmunity, CellularImmunologic MemoryEpidermal CellsJournal article002012345610.4049/jimmunol.12007090003119958000182-s2.0-8487112153722333McColl, S. [0000-0003-0949-4660]