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)alpha and interleukin (IL)-1 beta (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)gamma, TNF alpha, perforin and granzyme B compared to those primed by mDC(neu). T cells primed by CCL16/ mDC(neu) release IFN gamma in response to human HER-2(+) cells and kill human HER-2(+) target cells more efficiently than those primed by mDCneu. 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.
CCL16 enhances the CD8+ and CD4+ T cell reactivity to human HER-2 elicited by dendritic cells loaded with rat ortholog HER-2
AMICI, Augusto;MARCHINI, Cristina;
2008-01-01
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)alpha and interleukin (IL)-1 beta (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)gamma, TNF alpha, perforin and granzyme B compared to those primed by mDC(neu). T cells primed by CCL16/ mDC(neu) release IFN gamma in response to human HER-2(+) cells and kill human HER-2(+) target cells more efficiently than those primed by mDCneu. 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
