| First Author | Sato K | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 1 | Pages | 138-148 |
| PubMed ID | 28539430 | Mgi Jnum | J:254544 |
| Mgi Id | MGI:6100077 | Doi | 10.4049/jimmunol.1602005 |
| Citation | Sato K, et al. (2017) Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4(+) T Cells. J Immunol 199(1):138-148 |
| abstractText | Immune aging may underlie various aging-related disorders, including diminished resistance to infection, chronic inflammatory disorders, and autoimmunity. PD-1(+) and CD153(+) CD44(high) CD4(+) T cells with features of cellular senescence, termed senescence-associated T (SA-T) cells, increasingly accumulate with age and may play a role in the immune aging phenotype. In this article, we demonstrate that, compared with young mice, the aged mouse environment is highly permissive for spontaneous proliferation of transferred naive CD4(+) T cells, and it drives their transition to PD-1(+) and CD153(+) CD44(high) CD4(+) T cells after extensive cell divisions. CD4(+) T cells with essentially the same features as SA-T cells in aged mice are also generated from naive CD4(+) T cells after extensive cell divisions under severe T-lymphopenic conditions by gamma irradiation or in developmental T cell defect, often in association with spontaneous germinal centers, as seen in aged mice. The increase in SA-T cells is significantly enhanced after thymectomy at the young adult stage, along with accelerated T cell homeostatic proliferation, whereas embryonic thymus implantation in the late adult stage markedly restricts the homeostatic proliferation of naive CD4(+) T cells in the host and delays the increase in SA-T cells. Our results suggest that reduced T cell output due to physiologic thymic involution underlies the age-dependent accumulation of SA-T cells as a result of increasing homeostatic proliferation of naive CD4(+) T cells. SA-T cells may provide a suitable biomarker of immune aging, as well as a potential target for controlling aging-related disorders. |
