PT  - JOURNAL ARTICLE
AU  - Holthaus, Lisa
AU  - Sharma, Virag
AU  - Brandt, Daniel
AU  - Ziegler, Anette-Gabriele
AU  - Jastroch, Martin
AU  - Bonifacio, Ezio
TI  - Functional and metabolic fitness of human CD4<sup>+</sup> T lymphocytes during metabolic stress
AID  - 10.26508/lsa.202101013
DP  - 2021 Dec 01
TA  - Life Science Alliance
PG  - e202101013
VI  - 4
IP  - 12
4099  - http://www.life-science-alliance.org/content/4/12/e202101013.short
4100  - http://www.life-science-alliance.org/content/4/12/e202101013.full
SO  - Life Sci. Alliance2021 Dec 01; 4
AB  - Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T-cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, whereas early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T-cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T-cell proliferation, but not T-cell activation. Conditions that inhibited T-cell activation were associated with the down-regulation of 2′,5′-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T-cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress, and/or the function of T cells in these conditions will improve the efficacy of T-cell–based therapies.