Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging.
Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging.
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DOI：
10.1084/jem.20090896
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发表时间：
2009-08-31
期刊：
影响因子：
--
通讯作者：
Akbar AN
中科院分区：
文献类型：
--
作者：
Agius E;Lacy KE;Vukmanovic-Stejic M;Jagger AL;Papageorgiou AP;Hall S;Reed JR;Curnow SJ;Fuentes-Duculan J;Buckley CD;Salmon M;Taams LS;Krueger J;Greenwood J;Klein N;Rustin MH;Akbar AN
随着年龄的增长，免疫力会下降，然而，这种下降的机制尚不清楚。在这项研究中，我们发现老年人对召回抗原的皮肤迟发性超敏反应(DTH)显著降低。然而，这与CC趋化因子受体4、皮肤淋巴细胞相关抗原或CD4+T细胞的CD11a表达或其身体迁移能力无关。相反，老年人皮肤血管的激活有缺陷，这是由于巨噬细胞分泌肿瘤坏死因子-α减少所致。这可以防止记忆T细胞在抗原攻击后进入皮肤。然而，体外培养的皮肤巨噬细胞在TLR1/2或TLR4配体刺激下，可被诱导分泌肿瘤坏死因子-α，表明该缺陷是可逆的。因此，巨噬细胞衍生的细胞因子对组织微环境的调节减少可能导致记忆T细胞的免疫监视功能缺陷。这可能是皮肤在衰老过程中发生恶性肿瘤和感染的一个诱因。
Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging.
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DOI：
10.1084/jem.20011502
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Campbell DJ;Butcher EC
通讯作者：
Butcher EC
影响因子：
64.8
作者：
Fuhlbrigge, RC;Kieffer, JD;Kupper, TS
通讯作者：
Kupper, TS
DOI：
10.1038/nri1310
发表时间：
2004-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Kupper TS;Fuhlbrigge RC
通讯作者：
Fuhlbrigge RC
DOI：
10.1084/jem.174.6.1461
发表时间：
1991-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Berg EL;Yoshino T;Rott LS;Robinson MK;Warnock RA;Kishimoto TK;Picker LJ;Butcher EC
通讯作者：
Butcher EC
影响因子：
4.4
作者：
ENGELHARDT, B;CONLEY, FK;BUTCHER, EC
通讯作者：
BUTCHER, EC