Cargando…
Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells
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 activat...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582898/ https://www.ncbi.nlm.nih.gov/pubmed/32385048 http://dx.doi.org/10.4049/immunohorizons.2000020 |
_version_ | 1784812948482424832 |
---|---|
author | Presnell, Steven R. Spear, Henry K. Durham, Jerika Riddle, Tyce Applegate, Austin Lutz, Charles T. |
author_facet | Presnell, Steven R. Spear, Henry K. Durham, Jerika Riddle, Tyce Applegate, Austin Lutz, Charles T. |
author_sort | Presnell, Steven R. |
collection | PubMed |
description | 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-γ. NK cells were relatively fuel resilient and used Glc, glutamine (Gln), fatty acid, or acetate to power IFN-γ 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-γ production. |
format | Online Article Text |
id | pubmed-9582898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-95828982022-10-20 Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells Presnell, Steven R. Spear, Henry K. Durham, Jerika Riddle, Tyce Applegate, Austin Lutz, Charles T. Immunohorizons Article 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-γ. NK cells were relatively fuel resilient and used Glc, glutamine (Gln), fatty acid, or acetate to power IFN-γ 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-γ production. 2020-05-08 /pmc/articles/PMC9582898/ /pubmed/32385048 http://dx.doi.org/10.4049/immunohorizons.2000020 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Article Presnell, Steven R. Spear, Henry K. Durham, Jerika Riddle, Tyce Applegate, Austin Lutz, Charles T. Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells |
title | Differential Fuel Requirements of Human NK Cells and Human CD8 T
Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T
Cells |
title_full | Differential Fuel Requirements of Human NK Cells and Human CD8 T
Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T
Cells |
title_fullStr | Differential Fuel Requirements of Human NK Cells and Human CD8 T
Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T
Cells |
title_full_unstemmed | Differential Fuel Requirements of Human NK Cells and Human CD8 T
Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T
Cells |
title_short | Differential Fuel Requirements of Human NK Cells and Human CD8 T
Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T
Cells |
title_sort | differential fuel requirements of human nk cells and human cd8 t
cells: glutamine regulates glucose uptake in strongly activated cd8 t
cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582898/ https://www.ncbi.nlm.nih.gov/pubmed/32385048 http://dx.doi.org/10.4049/immunohorizons.2000020 |
work_keys_str_mv | AT presnellstevenr differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells AT spearhenryk differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells AT durhamjerika differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells AT riddletyce differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells AT applegateaustin differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells AT lutzcharlest differentialfuelrequirementsofhumannkcellsandhumancd8tcellsglutamineregulatesglucoseuptakeinstronglyactivatedcd8tcells |