Autophagy in T Cell Function and Aging

Abstract

Dysregulation of autophagy with age has been identified as a central mechanism of aging affecting many cells and tissues. T cells do also show decreased activity with age of different autophagic pathways. Here, we will review the current knowledge of the different functions that autophagy has in the regulation of T cell homeostasis, differentiation and function and explore how the age-associated decreased in autophagy activity may contribute to the altered T cell responses that characterize T cell immunosenescence.

Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses

“…Several studies have addressed the induction of autophagy by antigenic stimulation in murine T cells in vivo and in response to anti-CD3/CD28 in vitro stimulation of human T cells 23 . In mouse studies Xu et al measured a peak in autophagy induction shortly after the CD8+ effector phase with subsequent failure to mount memory responses 11 .…”

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

“…Importantly, decreased or dysregulated CMA with age in T cells, which also occurs in macroautophagy, may translate into altered quality control, energy balance and proteome remodeling. Therefore, it would be also important to consider the age to modulate autophagy in future therapies of GB that may affect T cells [20].…”

“…Autophagy maintains the energy demands of the metabolism of CD4 + T cells, contributing to sustain adenosine triphosphate (ATP) production in response to TCR engagement, proper anaerobic glycolysis and mitochondrial respiration [133,134]. Autophagy-related (ATG) proteins-dependent autophagic pathways also modulates T cell differentiation and function, regulating the generation of different T cell populations [20]. Autophagy is also needed in FOXP3 + regulatory T cells (Treg) to suppress anti-tumor immune responses, maintaining Treg cell homeostasis by prevention of metabolic alterations that decrease their survival and may lead to autoimmunity [137].…”

“…Autophagy keeps the homeostasis of immune cells and modulates the response to stressful stimuli. Autophagy regulates specific immune functions such as antigen presentation, cell activation and differentiation [17][18][19][20]. Thus, as it occurs with anti-cancer direct therapies, the use of autophagy modulators may affect the effectiveness of the current immunotherapies, and could strengthen the immune system to eliminate the cancer cells [21][22][23].…”

The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation

“…Endogenously, autophagy is essential for T-cell activation and differentiation in response to environmental insults. Dysregulation of autophagy and an increase of senescence during aging of T cells results in a compromised immune response to pathogens in the elderly (95). Exogenously, through SASP secretion, senescent cells can regulate immune infiltration and clearance of tumor cells, while autophagy contributes to immune cell function and cytokine production (72,96).…”