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Physiology and pathology of T-cell aging
Acquired immune function shows recognizable changes over time with organismal aging. These changes include T-cell dysfunction, which may underlie diminished resistance to infection and possibly various chronic age-associated diseases in the elderly. T-cell dysfunction may occur at distinct stages, f...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150735/ https://www.ncbi.nlm.nih.gov/pubmed/31967307 http://dx.doi.org/10.1093/intimm/dxaa006 |
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author | Minato, Nagahiro Hattori, Masakazu Hamazaki, Yoko |
author_facet | Minato, Nagahiro Hattori, Masakazu Hamazaki, Yoko |
author_sort | Minato, Nagahiro |
collection | PubMed |
description | Acquired immune function shows recognizable changes over time with organismal aging. These changes include T-cell dysfunction, which may underlie diminished resistance to infection and possibly various chronic age-associated diseases in the elderly. T-cell dysfunction may occur at distinct stages, from naive cells to the end stages of differentiation during immune responses. The thymus, which generates naive T cells, shows unusually early involution resulting in progressive reduction of T-cell output after adolescence, but peripheral T-cell numbers are maintained through antigen-independent homeostatic proliferation of naive T cells driven by the major histocompatibility complex associated with self-peptides and homeostatic cytokines, retaining the diverse repertoire. However, extensive homeostatic proliferation may lead to the emergence of dysfunctional CD4(+) T cells with features resembling senescent cells, termed senescence-associated T (SA-T) cells, which increase and accumulate with age. In situations such as chronic viral infection, T-cell dysfunction may also develop via persistent antigen stimulation, termed exhaustion, preventing possible immunopathology due to excessive immune responses. Exhausted T cells are developed through the effects of checkpoint receptors such as PD-1 and may be reversed with the receptor blockade. Of note, although defective in their regular T-cell antigen-receptor-mediated proliferation, SA-T cells secrete abundant pro-inflammatory factors such as osteopontin, reminiscent of an SA-secretory phenotype. A series of experiments in mouse models indicated that SA-T cells are involved in systemic autoimmunity as well as chronic tissue inflammation following tissue stresses. In this review, we discuss the physiological aspects of T-cell dysfunction associated with aging and its potential pathological involvement in age-associated diseases and possibly cancer. |
format | Online Article Text |
id | pubmed-7150735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71507352020-04-15 Physiology and pathology of T-cell aging Minato, Nagahiro Hattori, Masakazu Hamazaki, Yoko Int Immunol Invited Review Acquired immune function shows recognizable changes over time with organismal aging. These changes include T-cell dysfunction, which may underlie diminished resistance to infection and possibly various chronic age-associated diseases in the elderly. T-cell dysfunction may occur at distinct stages, from naive cells to the end stages of differentiation during immune responses. The thymus, which generates naive T cells, shows unusually early involution resulting in progressive reduction of T-cell output after adolescence, but peripheral T-cell numbers are maintained through antigen-independent homeostatic proliferation of naive T cells driven by the major histocompatibility complex associated with self-peptides and homeostatic cytokines, retaining the diverse repertoire. However, extensive homeostatic proliferation may lead to the emergence of dysfunctional CD4(+) T cells with features resembling senescent cells, termed senescence-associated T (SA-T) cells, which increase and accumulate with age. In situations such as chronic viral infection, T-cell dysfunction may also develop via persistent antigen stimulation, termed exhaustion, preventing possible immunopathology due to excessive immune responses. Exhausted T cells are developed through the effects of checkpoint receptors such as PD-1 and may be reversed with the receptor blockade. Of note, although defective in their regular T-cell antigen-receptor-mediated proliferation, SA-T cells secrete abundant pro-inflammatory factors such as osteopontin, reminiscent of an SA-secretory phenotype. A series of experiments in mouse models indicated that SA-T cells are involved in systemic autoimmunity as well as chronic tissue inflammation following tissue stresses. In this review, we discuss the physiological aspects of T-cell dysfunction associated with aging and its potential pathological involvement in age-associated diseases and possibly cancer. Oxford University Press 2020-01-22 /pmc/articles/PMC7150735/ /pubmed/31967307 http://dx.doi.org/10.1093/intimm/dxaa006 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Society for Immunology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Invited Review Minato, Nagahiro Hattori, Masakazu Hamazaki, Yoko Physiology and pathology of T-cell aging |
title | Physiology and pathology of T-cell aging |
title_full | Physiology and pathology of T-cell aging |
title_fullStr | Physiology and pathology of T-cell aging |
title_full_unstemmed | Physiology and pathology of T-cell aging |
title_short | Physiology and pathology of T-cell aging |
title_sort | physiology and pathology of t-cell aging |
topic | Invited Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150735/ https://www.ncbi.nlm.nih.gov/pubmed/31967307 http://dx.doi.org/10.1093/intimm/dxaa006 |
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