Mitochondrial Oxidative Stress in Aging CD4+ T cells

Identification: Headley, Colwyn


Description

Mitochondrial Oxidative Stress in Aging CD4+ T cells
 
Colwyn A. Headley, Varun Dwivedi, Joanne Turner
Texas Biomedical Research Institute, 78227, USA;  Ohio State University, 43210, USA
 
Mitochondria play a critical role in adaptive immunity by dynamically influencing the response of T cells through glucose and fatty acid metabolism, Ca2+ buffering, and redox signaling via production of reactive oxygen species (ROS). Adaptive immunity wanes with increasing biological age. However, how biological aging alters mitochondrial dynamics in CD4+ T cells is unclear. We hypothesize that dysfunctional mitochondria are directly contributing to abnormal cytokine signaling, and pro-inflammatory/oxidative stressed status of CD4+ T cells. Our project aimed to ascertain the effects of aging on cellular and mitochondrial oxidative stress of CD4+ T in old (18 month) and young (3 month) mice. Splenic CD4+ T cells were magnetically isolated from old and young mice, after which purified CD4+ T cells were assessed by flow cytometry analysis for intracellular ROS and Ca2+ levels, mitochondrial viability, and neutral lipids, basally and after activation with α-CD3/CD28 or with phorbol 12-myristate 13-acetate (PMA)/ionomycin(IONO) stimulation. Compared to young mice, splenic CD4+ T cells from old mice had higher levels of NO and mitochondrial ROS, both basally and after stimulation. CD4+ T cells isolated from old mice had similar neutral lipid content (as compared to young mice), but significantly less active mitochondria. This is suggestive of altered mitochondrial function. Our data also show increased levels of cytosolic Ca2+ in aged CD4+ T cells (compared to young T cells), and higher ratios of mitochondrial Ca2+ to mitochondrial mass, indicative of Ca2+ overloading. In general, CD4+ T cells isolated from old mice have increased level of oxidative stress.
 

 
 

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