論文

査読有り 国際誌
2020年1月22日

Physiology and pathology of T-cell aging.

International immunology
  • Nagahiro Minato
  • ,
  • Masakazu Hattori
  • ,
  • Yoko Hamazaki

32
4
開始ページ
223
終了ページ
231
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/intimm/dxaa006

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 complexed 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 (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, possibly preventing 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. Although defective in their regular T-cell antigen-receptor-mediated proliferation, SA-T cells secrete abundant proinflammatory factors such as osteopontin, reminiscent of 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.

リンク情報
DOI
https://doi.org/10.1093/intimm/dxaa006
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31967307
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150735
ID情報
  • DOI : 10.1093/intimm/dxaa006
  • PubMed ID : 31967307
  • PubMed Central 記事ID : PMC7150735

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