A Combination of Local Inflammation and Central Memory T Cells Potentiates Immunotherapy in the Skin

  • Fiorenza S
  • Kenna T
  • Comerford I
  • et al.
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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.

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Fiorenza, S., Kenna, T. J., Comerford, I., McColl, S., Steptoe, R. J., Leggatt, G. R., & Frazer, I. H. (2012). A Combination of Local Inflammation and Central Memory T Cells Potentiates Immunotherapy in the Skin. The Journal of Immunology, 189(12), 5622–5631. https://doi.org/10.4049/jimmunol.1200709

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