Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 37, Pages 15807-15812Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0908805106
Keywords
immunosenescence; osteopontin
Categories
Funding
- Japanese Ministry of Education, Culture, Science, Sports and Technology
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [19059008, 19059009, 20200069] Funding Source: KAKEN
Ask authors/readers for more resources
Although altered T cell function plays a part in immunosenescence, the mechanisms remain uncertain. Here we identify a bona fide age-dependent PD-1(+) memory phenotype (MP) CD4(+) T cell sub-population that hardly proliferates in response to T cell receptor (TCR) stimulation and produces abundant osteopontin at the cost of typical T cell lymphokines. These T cells demonstrate impaired repopulation in Rag2(-/-) mice, but a homeostatic proliferation in gamma-ray-irradiated mice. These T cells also reveal a unique molecular signature, including a strong expression of C/EBP alpha normally expressed in myeloid-lineage cells, with diminished c-Myc and cyclin D1. Transduction of Cebpa in regular CD4(+) T cells inhibited the TCR-mediated proliferation with c-Myc and cyclin D1 repression and caused a striking activation of Spp1 encoding osteopontin along with concomitant repression of T cell lymphokine genes. Although these T cells gradually increase in number with age and become predominant at the senescent stage in normal mice, the generation is robustly accelerated during leukemia. In both conditions, their predominance is associated with the diminution of specific CD4(+) T cell response. The results suggest that global T cell immunodepression in senescence and leukemia is attributable to the increase in PD-1(+) MP CD4(+) T cells expressing C/EBP alpha.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available