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https://hdl.handle.net/2440/75131
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dc.contributor.author | Fiorenza, S. | - |
dc.contributor.author | Kenna, T. | - |
dc.contributor.author | Comerford, I. | - |
dc.contributor.author | McColl, S. | - |
dc.contributor.author | Steptoe, R. | - |
dc.contributor.author | Leggatt, G. | - |
dc.contributor.author | Frazer, I. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Journal of Immunology, 2012; 189(12):5622-5631 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | http://hdl.handle.net/2440/75131 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Salvatore Fiorenza, Tony J. Kenna, Iain Comerford, Shaun McColl, Raymond J. Steptoe, Graham R. Leggatt, and Ian H. Frazer | - |
dc.language.iso | en | - |
dc.publisher | Amer Assoc Immunologists | - |
dc.rights | Copyright © 2012 by The American Association of Immunologists, Inc | - |
dc.source.uri | http://dx.doi.org/10.4049/jimmunol.1200709 | - |
dc.subject | Epidermis | - |
dc.subject | T-Lymphocyte Subsets | - |
dc.subject | Cells, Cultured | - |
dc.subject | Skin | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred C57BL | - |
dc.subject | Mice, Transgenic | - |
dc.subject | Mice, Knockout | - |
dc.subject | Mice | - |
dc.subject | Inflammation | - |
dc.subject | Adoptive Transfer | - |
dc.subject | Skin Transplantation | - |
dc.subject | Cell Communication | - |
dc.subject | Immune Tolerance | - |
dc.subject | Immunity, Cellular | - |
dc.subject | Immunologic Memory | - |
dc.subject | Epidermal Cells | - |
dc.title | A Combination of Local Inflammation and Central Memory T Cells Potentiates Immunotherapy in the Skin | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.4049/jimmunol.1200709 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | McColl, S. [0000-0003-0949-4660] | - |
Appears in Collections: | Aurora harvest 4 IPAS publications Molecular and Biomedical Science publications |
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