| First Author | Fiorenza S | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 12 | Pages | 5622-31 |
| PubMed ID | 23144496 | Mgi Jnum | J:279550 |
| Mgi Id | MGI:6363396 | Doi | 10.4049/jimmunol.1200709 |
| Citation | Fiorenza S, et al. (2012) A combination of local inflammation and central memory T cells potentiates immunotherapy in the skin. J Immunol 189(12):5622-31 |
| abstractText | 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. |
