People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells

• Published in: Scientific reports Vol. 12; no. 1; p. 11425
• Main Authors: van Eekeren, Louise E., Matzaraki, Vasiliki, Zhang, Zhenhua, van de Wijer, Lisa, Blaauw, Marc J. T., de Jonge, Marien I., Vandekerckhove, Linos, Trypsteen, Wim, Joosten, Leo A. B., Netea, Mihai G., de Mast, Quirijn, Koenen, Hans J. P. M., Li, Yang, van der Ven, André J. A. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-07-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/1619/554/1834; 631/250/255; 631/250/98; 692/699/255/1901; Antiretroviral agents; Antiretroviral therapy; CCR5 protein; CD4 antigen; CD8 antigen; Deoxyribonucleic acid; DNA; Energy demand; Energy metabolism; Flow cytometry; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Immunoregulation; Lymphocytes; Lymphocytes T; Metabolic pathways; Metabolites; Monocytes; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-15646-0

CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls. Percentages of CCR5+ cells (%) and CCR5 mean fluorescence intensity assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites. Metabolic pathways were identified. PLHIV displayed higher percentages of CCR5+ monocytes and several CD8+ T cell subsets, but lower percentages of CCR5+ naive CD4+ T cells and regulatory T cells (Tregs). HIV-1 CA-DNA and CA-RNA correlated positively with percentages of CCR5+ lymphocytes. Metabolome analysis revealed three pathways involved in energy metabolism associated with percentage of CCR5+ CD8+ T cells in PLHIV. Our results indicate that CCR5 is differently expressed on various circulating immune cells in PLHIV. Hence, cell-trafficking of CD8+ T cells and Tregs may be altered in PLHIV. Associations between energy pathways and percentage of CCR5+ CD8+ T cells in PLHIV suggest higher energy demand of these cells in PLHIV.