PD-1+memory phenotype CD4+T cells expressing C/EBPα underlie T cell immunodepression in senescence and leukemia

• DOI: 10.1073/pnas.0908805106
• Publication Date: 2009-09-09T02:20:39Z
• Authors: Kenichiro Shimatani; Yasuhiro Nakashima; Masakazu Hattori; Yoko Hamazaki; Nagahiro Minato
• Keywords: Senescence

Although altered T cell function plays a part in immunosenescence, the mechanisms remain uncertain. Here we identify bona fide age-dependent PD-1(+) memory phenotype (MP) CD4(+) subpopulation that hardly proliferates response to receptor (TCR) stimulation and produces abundant osteopontin at cost of typical lymphokines. These cells demonstrate impaired repopulation Rag2(-/-) mice, but homeostatic proliferation gamma-ray-irradiated mice. also reveal unique molecular signature, including strong expression C/EBPalpha normally expressed myeloid-lineage cells, with diminished c-Myc cyclin D1. Transduction Cebpa regular inhibited TCR-mediated D1 repression caused striking activation Spp1 encoding along concomitant lymphokine genes. these gradually increase number age become predominant senescent stage normal generation is robustly accelerated during leukemia. In both conditions, their predominance associated diminution specific response. The results suggest global immunodepression senescence leukemia attributable MP expressing C/EBPalpha.