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Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells

Yukiko Shimada1, Masami Hayashi, Yasuhiko Nagasaka

  • 1Cellular Signaling Group, Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, Japan.

Experimental Gerontology
|May 22, 2009
PubMed

Insights

Aging increases negative co-stimulatory receptors like PD-1 on T cells, impairing their function. This study suggests PD-1 up-regulation contributes to age-related T-cell decline, particularly in effector-memory cells.

Area of Science:

  • Immunology
  • Aging Research
  • Cellular Biology

Background:

  • T-cell function declines with age, impacting immunity.
  • Co-stimulatory receptors regulate T-cell receptor (TCR) signaling.
  • The role of co-stimulatory receptors in age-associated T-cell dysfunction is unclear.

Purpose of the Study:

  • To investigate the involvement of co-stimulatory receptors in age-related T-cell functional decline.
  • To analyze changes in T-cell co-stimulatory receptor expression during aging in mice.

Main Methods:

  • Analysis of mRNA and protein expression of CTLA-4, PD-1, and CD28 in mouse CD4(+) T cells.
  • Flow cytometry to assess surface receptor expression on T cells.
  • Evaluation of T-cell proliferation in aged mice.

Main Results:

  • CTLA-4 and PD-1 (negative co-stimulatory receptors) mRNA and protein levels increased with aging.
  • CD28 (positive regulatory receptor) expression remained unchanged.
  • PD-1 was highly expressed on aged T cells, especially effector-memory T cells.
  • PD-1-expressing T cells from old mice showed reduced proliferation.

Conclusions:

  • Increased PD-1 expression on T cells is associated with aging.
  • Up-regulation of PD-1 may contribute to the age-dependent decline in effector-memory T-cell function.
  • Targeting PD-1 could potentially restore T-cell function in aged individuals.

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