Skin Tumor Responsiveness to IL-2 Treatment Correlates to CD8 Treg Expansion in an Immunocompetent Mouse Model. (100.15)
| Autor: | David Foureau, Iain McKillop, Chase Jones, Asim Amin, Richard White, Jonathan Salo |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:100.15-100.15 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.184.supp.100.15 |
| Popis: | CD8 Tregs play an important role in graft tolerance and autoimmune disease status. Interleukin-2 (IL-2) induces Foxp3 expression by activated human CD8 T cells in vitro, and expands circulating CD8 Foxp3+ T cells in melanoma patients. IL-2 is FDA approved for the treatment of advanced melanoma, yet positive outcomes are limited. The aim of this study was to determine the phenotype and distribution of CD8 Foxp3 expressing T cells in skin tumor-bearing mice receiving IL-2. In normal or skin tumor-bearing mice, Foxp3 expressing CD8 T cells were a rare but naturally occurring cell subset. Primarily located in skin-draining lymph nodes CD8 Foxp3+ T cell expressed both activated CTL (CD28+, CD44+) and Treg (CTLA4+, PD1lo, NKG2Alo) markers. Following high dose IL-2 treatment, a dramatic increase in CD8 Treg prevalence was observed in a subcutaneous-tumor model that is non-responsive to IL-2 treatment (B16-F10 melanoma cell line). Furthermore, distribution analysis in this (B16-F10) model demonstrated increased CD8 Treg expression in the circulation and tumor-draining lymph nodes. Conversely, in the IL-2 responsive MCA-205 fibrosarcoma-bearing mouse model no significant changes in CD8 Treg were measured, either in the bloodstream or within the tumor-draining lymph nodes. In conclusion, this study characterized CD8 Foxp3+ T cells (CD8 Treg) as a new immunosuppressive cell subset, the expansion of which was associated with skin tumor that failed to respond to IL-2 treatment. |
| Databáze: | OpenAIRE |
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