| First Author | Norrie IC | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e84728 |
| PubMed ID | 24404186 | Mgi Jnum | J:212211 |
| Mgi Id | MGI:5578297 | Doi | 10.1371/journal.pone.0084728 |
| Citation | Norrie IC, et al. (2014) C/EBPalpha is dispensable for the ontogeny of PD-1+ CD4+ memory T cells but restricts their expansion in an age-dependent manner. PLoS One 9(1):e84728 |
| abstractText | Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPalpha has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPalpha could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPalpha for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPalpha expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPalpha repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPalpha-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPalpha in immunosenescence, these findings efficiently discard the potential of using C/EBPalpha as a target for the alleviation of ageing/cancer-associated immunosenescence. |
