CCL16 Enhances the CD8+ and CD4+ T Cell Reactivity to Human Her-2 Elicited by Dendritic Cells Loaded with Rat Ortholog Her-2

Abstract

T cells from HLA A2+ healthy donors were co-cultured with autologous dendritic cells (DC) loaded with apoptotic tumor cells expressing rat neu, and were induced to mature by tumor necrosis factor (TNF)α and interleukin (IL)-1β (mDC neu) or by the CCL16 chemokine (CCL16/mDC neu). Priming by CCL16/mDC neu induces a larger population of T cells that express cytoplasmatic interferon (IFN)γ, TNFα, perforin and granzyme B compared to those primed by mDC neu. T cells primed by CCL16/mDC neu release IFNγ in response to human HER-2+ cells and kill human HER-2+ target cells more efficiently than those primed by mDC neu. Our results show that both the loading of DC with xenogeneic rat neu and their maturation by CCL16 are two issues of critical importance for the elicitation of an effective response to human HER-2 in T cells from normal donors.