Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Masson, Jesse J.R., Murphy, Andrew J., Lee, Man K.S., Ostrowski, Matias, Crowe, Suzanne M., and Palmer, Clovis S. (2017) Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy. PLoS ONE, 12 (8). e0183931.

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Abstract

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 mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

Item ID: 54078
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Australian Centre for HIV and Hepatitis Virology Research (ACHHVR), University of Washington Center for AIDS Research (CFAR), National Institute of Health (NIH), USA
Projects and Grants: ACHHVR ACH2, CFAR 2010 development grant, NIH award number AI027757
Date Deposited: 15 Jun 2018 00:08
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 60%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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