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Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4(+) T cells during aging

Agius, E; Lacy, KE; Vukmanovic-Stejic, M; Jagger, AL; Papageorgiou, AP; Hall, S; Reed, JR; ... Akbar, AN; + view all (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4(+) T cells during aging. The Journal of Experimental Medicine , 206 (9) 1929 - 1940. 10.1084/jem.20090896. Green open access

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Abstract

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-alpha 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-alpha 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.

Type: Article
Title: Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4(+) T cells during aging
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20090896
Publisher version: http://dx.doi.org/10.1084/jem.20090896
Language: English
Additional information: © 2009 Agius et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). This provides the non-exclusive right to copy, distribute, or display the Work is granted after six months of publication.
Keywords: Experimental autoimmune encephalomyelitis, microvascular endothelial-cells, delayed-type hypersensitivity, tumor-necrosis-factor, dendritic cells, in-vivo, rheumatoid-arthritis, adhesion molecule-1, lymphocyte antigen, cutting edge
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/141059
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