title: IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age.
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.
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Hirotake
authors: H
authors: Tsukamoto
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Satoru
authors: S
authors: Senju
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Keiko
authors: K
authors: Matsumura
authors: Department of Pathology, University of Massachusetts Medical School, 335 Plantation Street, Worcester, Massachusetts 01655, USA.
authors: Susan L
authors: SL
authors: Swain
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Yasuharu
authors: Y
authors: Nishimura
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D005354:Fibrosarcoma / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D051257:Proto-Oncogene Proteins c-maf / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019139:Tumor Escape; D000098546:Interleukin-21
chemical_list: C556062:IL10 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D000098546:Interleukin-21