IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age

Citations Over TimeTop 10% of 2015 papers

Abstract

Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4(+) T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4(+) T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4(+) T cells to promote CD8(+) T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4(+) T cells in aged mice, causing attenuated responses of CD8(+) T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4(+) T-cell-mediated immunity against tumour in old age.

Related Papers

• → EFFECT OF THE NEMATODE PHASMARHABDITIS HERMAPHRODITA ON YOUNGSTAGES OF THE PEST SLUG ARION LUSITANICUS(2002)40 cited
• → Cloning and Characterization of Rat BAT3 cDNA(1999)20 cited
• → Anthoxanthum Mosaic Virus(1970)6 cited
• → HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53(2007)127 cited
• → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)