Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells.
To explore whether any co-stimulatory receptor(s) for TCR signaling is involved in the age-associated decline in T-cell function, we analyzed changes in these receptors in freshly isolated mouse CD4(+) T cells during aging. Both the mRNA and protein expression levels of CTLA-4 and PD-1, negative co-stimulatory receptors, increase with aging. No such changes are observed for CD28, a positive regulatory receptor. PD-1 is highly expressed on the surface of old, but not young, mouse T cells, while the level of surface-expressed CTLA-4 is very low regardless of age. PD-1 is preferentially expressed on the surface of effector-memory (CD44(hi)CD62L(lo)) T cells, a subset that increases with aging. CD4(+)PD-1(+) T cells from old mice exhibit proliferative hyporesponsiveness. These results suggest that the up-regulation of surface-expressed PD-1 may cause the age-dependent functional decline in effector-memory T cells.
Shimada
Yukiko
Y
Cellular Signaling Group, Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, Japan.
Hayashi
Masami
M
Nagasaka
Yasuhiko
Y
Ohno-Iwashita
Yoshiko
Y
Inomata
Mitsushi
M
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D007156:Immunologic Memory / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D015854:Up-Regulation
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor