TY - JOUR
T1 - Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells
T2 - Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells
AU - Presnell, Steven R.
AU - Spear, Henry K.
AU - Durham, Jerika
AU - Riddle, Tyce
AU - Applegate, Austin
AU - Lutz, Charles T.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/5/1
Y1 - 2020/5/1
N2 - CD8 T cells and NK cells are the two major cytotoxic lymphocytes that carry out cell-mediated immunity and regulate other immune responses. However, we do not completely understand human CD8 T cell and NK cell metabolic requirements and they have not been compared in the same experiments. We activated human CD8 T cells by two anti–CD3/CD28 mAb methods, and we stimulated both CD8 T cells and NK cells with IL-12/IL-18. When glucose (Glc) could not be used, human CD8 T cells either died or became hypofunctional, depending upon the anti–CD3/CD28 activation method. In contrast, Glc starvation did not decrease the percentage of IL-12/IL-18–stimulated human NK cells that made IFN-g. NK cells were relatively fuel resilient and used Glc, glutamine (Gln), fatty acid, or acetate to power IFN-g expression. Surprisingly, strongly activated human CD8 T cells required Gln for glycolysis and Glc uptake. We showed that human CD8 T cells regulate Glc uptake by a novel mechanism related to the TXNIP pleiotropic protein. These conditions may be relevant to septic patients who have high blood Glc but low Gln. Under the conditions tested, Gln did not change human NK cell TXNIP expression. Our experiments reveal fundamental differences in human CD8 T cell and NK cell metabolism and the fuels needed for IFN-g production.
AB - CD8 T cells and NK cells are the two major cytotoxic lymphocytes that carry out cell-mediated immunity and regulate other immune responses. However, we do not completely understand human CD8 T cell and NK cell metabolic requirements and they have not been compared in the same experiments. We activated human CD8 T cells by two anti–CD3/CD28 mAb methods, and we stimulated both CD8 T cells and NK cells with IL-12/IL-18. When glucose (Glc) could not be used, human CD8 T cells either died or became hypofunctional, depending upon the anti–CD3/CD28 activation method. In contrast, Glc starvation did not decrease the percentage of IL-12/IL-18–stimulated human NK cells that made IFN-g. NK cells were relatively fuel resilient and used Glc, glutamine (Gln), fatty acid, or acetate to power IFN-g expression. Surprisingly, strongly activated human CD8 T cells required Gln for glycolysis and Glc uptake. We showed that human CD8 T cells regulate Glc uptake by a novel mechanism related to the TXNIP pleiotropic protein. These conditions may be relevant to septic patients who have high blood Glc but low Gln. Under the conditions tested, Gln did not change human NK cell TXNIP expression. Our experiments reveal fundamental differences in human CD8 T cell and NK cell metabolism and the fuels needed for IFN-g production.
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U2 - 10.4049/immunohorizons.2000020
DO - 10.4049/immunohorizons.2000020
M3 - Article
C2 - 32385048
AN - SCOPUS:85096393379
VL - 4
SP - 231
EP - 244
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 5
ER -