Negative Influence of Aging on Differentiation and Proliferation of CD8+ T-Cells in Dogs

Abstract

Immunosenescence is an age-related change in the immune system characterized by a reduction in naïve T-cells and an impaired proliferative capacity of CD8+ T-cells in older individuals. Recent research revealed the crucial impact of immunosenescence on the development and control of cancer, and aging is one of the causes that diminish the therapeutic efficacy of cancer immunotherapies targeting CD8+ T-cell activation. Despite dog cancer being defined as an age-related disease, there are few fundamental understandings regarding the relationship between aging and the canine immune system. Therefore, we aimed to elucidate the characteristics of immunosenescence in dogs and analyzed the effects of aging on the differentiation status and proliferation of canine CD8+ T cells using T-cell specific stimulation with anti-canine CD3/CD28 antibody-coated beads and interleukin-2. As a result, we found that older dogs have a lower proliferative capacity of CD8+ T-cells and a reduction in the naïve subset in their peripheral blood. Further analysis showed that older dogs had attenuated proliferation of the effector and central memory subsets. These results indicate the importance of maintaining less differentiated subsets to expand CD8+ T-cells in dogs and provide helpful insight into the development of dog immune therapies that require T-cell expansion ex vivo.

Betaine and L-Carnitine Synergistically Influence the Metabolome and Immune Response in Dogs

“…More recently, a lower proliferative capacity of CD8+ T cells in older dogs compared to younger dogs was reported [39]. It was shown in dogs that CD8+ cells play an important role in fighting infections and are active as antitumor agents [40]. These data suggest that further research investigating the effects of these dietary interventions on CD4+ and CD8+ cells and aging should bring valuable insight into optimizing immune responses in dogs.…”