Age-associated Alterations in T cell Output and Functions
Abstract Body: The elderly have a higher risk for a wide range of diseases, including infection, tumor, and cardiovascular disease. This could be, at least partially, attributed to T lymphocyte changes during aging. The goal of this project was to characterize age-related changes in T cell output and functions. In this study, young (3-6 months old) and aged (18-24 months old) male and female C57BL/6J mice were utilized. Our data showed that compared to young mice, aged mice demonstrated significantly smaller thymus and fewer developing thymocytes, including double negative CD4-CD8-, double positive CD4+CD8+, as well as single positive CD4+ and CD8+ thymocytes, which implies that aged mice generate less T cells. Accordingly, circulating T cell count was significantly lower in aged mice than young controls. To investigate how aging affects T cell functions, we isolated splenic T cells and stimulated them with PMA (100 nM) + ionomycin (1 µM) (P+I) or vehicle for 4 hours. At the steady state, aged T cells expressed higher levels of Ifng, Tnfα, granzyme b, and perforin than young T cells, suggesting that aged T cells show a senescence-associated secretory phenotype (SASP). After stimulation with P+I, both young and aged T cells expressed dramatically higher levels of Ifng, Tnfα, Il2, Il4, Il17, and granzyme b, indicative of T cell activation. Interestingly, aged T cells had higher expression of Ifng, Il17, and granzyme b, but lower Tnfα and Il2 levels. Moreover, aged T cells expressed higher levels of exhaustion markers, such as Pd1, Ctla4, Lag3, and Tigit, indicating that aged T cells exhibit an exhaustion phenotype. In conclusion, our study demonstrates that aged mice show smaller thymus and fewer thymocytes and blood T cells than young mice. In addition, aged T cells exhibit a SASP and exhaustion phenotype. Upon activation, aged T cells might be more cytotoxic by secreting higher levels of IFN-γ, IL-17, and granzyme B.
Konovalova, Daria
( University of South Florida
, Tampa
, Florida
, United States
)
Shane, Danielle
( University of South Florida
, Tampa
, Florida
, United States
)
Mabito, Megan
( University of South Florida
, Tampa
, Florida
, United States
)
Yuan, Sarah
( University of South Florida
, Tampa
, Florida
, United States
)
Ma, Yonggang
( University of South Florida
, Tampa
, Florida
, United States
)
Author Disclosures:
Daria Konovalova:DO NOT have relevant financial relationships
| Danielle Shane:DO NOT have relevant financial relationships
| Megan Mabito:DO NOT have relevant financial relationships
| Sarah Yuan:DO NOT have relevant financial relationships
| Yonggang Ma:DO NOT have relevant financial relationships