Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

Clovis Prince-Steve Palmer, Matias Ostrowski, Maelenn Gouillou, Louis Meng-Chin Tsai, Di Yu, Jingling Zhou, Darren C Henstridge, Anna Maisa, Anna C Hearps, Sharon R Lewin, Alan L Landay, Anthony Jaworowski, Joseph M McCune, Suzanne M Crowe

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Abstract

OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4 and CD8 T cells. DESIGN AND METHODS: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry. RESULTS: The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status. CONCLUSION: Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.
Original languageEnglish
Pages (from-to)297 - 309
Number of pages13
JournalAIDS
Volume28
Issue number3
DOIs
Publication statusPublished - 2014

Cite this

Palmer, Clovis Prince-Steve ; Ostrowski, Matias ; Gouillou, Maelenn ; Tsai, Louis Meng-Chin ; Yu, Di ; Zhou, Jingling ; Henstridge, Darren C ; Maisa, Anna ; Hearps, Anna C ; Lewin, Sharon R ; Landay, Alan L ; Jaworowski, Anthony ; McCune, Joseph M ; Crowe, Suzanne M. / Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection. In: AIDS. 2014 ; Vol. 28, No. 3. pp. 297 - 309.
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title = "Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection",
abstract = "OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4 and CD8 T cells. DESIGN AND METHODS: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry. RESULTS: The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status. CONCLUSION: Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.",
author = "Palmer, {Clovis Prince-Steve} and Matias Ostrowski and Maelenn Gouillou and Tsai, {Louis Meng-Chin} and Di Yu and Jingling Zhou and Henstridge, {Darren C} and Anna Maisa and Hearps, {Anna C} and Lewin, {Sharon R} and Landay, {Alan L} and Anthony Jaworowski and McCune, {Joseph M} and Crowe, {Suzanne M}",
year = "2014",
doi = "10.1097/QAD.0000000000000128",
language = "English",
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Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection. / Palmer, Clovis Prince-Steve; Ostrowski, Matias; Gouillou, Maelenn; Tsai, Louis Meng-Chin; Yu, Di; Zhou, Jingling; Henstridge, Darren C; Maisa, Anna; Hearps, Anna C; Lewin, Sharon R; Landay, Alan L; Jaworowski, Anthony; McCune, Joseph M; Crowe, Suzanne M.

In: AIDS, Vol. 28, No. 3, 2014, p. 297 - 309.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

AU - Palmer, Clovis Prince-Steve

AU - Ostrowski, Matias

AU - Gouillou, Maelenn

AU - Tsai, Louis Meng-Chin

AU - Yu, Di

AU - Zhou, Jingling

AU - Henstridge, Darren C

AU - Maisa, Anna

AU - Hearps, Anna C

AU - Lewin, Sharon R

AU - Landay, Alan L

AU - Jaworowski, Anthony

AU - McCune, Joseph M

AU - Crowe, Suzanne M

PY - 2014

Y1 - 2014

N2 - OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4 and CD8 T cells. DESIGN AND METHODS: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry. RESULTS: The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status. CONCLUSION: Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.

AB - OBJECTIVES: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4 and CD8 T cells. DESIGN AND METHODS: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry. RESULTS: The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status. CONCLUSION: Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.

UR - http://www.ncbi.nlm.nih.gov/pubmed/24335483

U2 - 10.1097/QAD.0000000000000128

DO - 10.1097/QAD.0000000000000128

M3 - Article

VL - 28

SP - 297

EP - 309

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 3

ER -