A combination of local inflammation and central memory T cells potentiates immunotherapy in the skin

Fiorenza, Salvatore, Kenna, Tony J., Comerford, Iain, McColl, Shaun, Steptoe, Raymond J., Leggatt, Graham R., & Frazer, Ian H. (2012) A combination of local inflammation and central memory T cells potentiates immunotherapy in the skin. Journal of Immunology, 189(12), pp. 5622-5631.

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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. Copyright © 2012 by The American Association of Immunologists, Inc.

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12 citations in Scopus
13 citations in Web of Science®
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ID Code: 94054
Item Type: Journal Article
Refereed: Yes
Keywords: imiquimod, interleukin 2, macrophage inflammatory protein 1beta, adoptive immunotherapy, adoptive transfer, animal experiment, animal model, article, CD8+ T lymphocyte, cell transfer, cellular immunity, controlled study, effector cell, ex vivo study, immunoregulation, in vivo study, inflammation, keratinocyte, lymphocyte function, lymphocyte subpopulation, memory T lymphocyte, mouse, nonhuman, phenotype, priority journal, process optimization, protein expression, reproducibility, transgene, Animals, Cell Communication, Cells, Cultured, Epidermis, Immune Tolerance, Immunity, Cellular, Immunologic Memory, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Skin, Skin Transplantation, T-Lymphocyte Subsets
DOI: 10.4049/jimmunol.1200709
ISSN: 1550-6606
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 by The American Association of Immunologists, Inc.
Deposited On: 21 Mar 2016 01:51
Last Modified: 22 Mar 2016 02:55

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