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|Title:||A Combination of Local Inflammation and Central Memory T Cells Potentiates Immunotherapy in the Skin|
|Citation:||Journal of Immunology, 2012; 189(12):5622-5631|
|Publisher:||Amer Assoc Immunologists|
|Salvatore Fiorenza, Tony J. Kenna, Iain Comerford, Shaun McColl, Raymond J. Steptoe, Graham R. Leggatt, and Ian H. Frazer|
|Abstract:||Adoptive 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.|
|Keywords:||Epidermis; T-Lymphocyte Subsets; Cells, Cultured; Skin; Animals; Mice, Inbred C57BL; Mice, Transgenic; Mice, Knockout; Mice; Inflammation; Adoptive Transfer; Skin Transplantation; Cell Communication; Immune Tolerance; Immunity, Cellular; Immunologic Memory|
|Rights:||Copyright © 2012 by The American Association of Immunologists, Inc|
|Appears in Collections:||Molecular and Biomedical Science publications|
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