Functional state of regulatory CD4+T cell pool in HIV/hepatitis C virus coinfected subjects

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Abstract

Coinfection with HIV and hepatitis C virus (HCV) leads to development of systemic inflammation associated with increased risk for liver, kidney and cardiovascular diseases, as well as higher mortality from AIDS-associated and non-AIDS-associated illnesses. To a large extent, systemic inflammation is controlled by regulatory T lymphocytes, a subset of CD4+ T cells. While expressing various functional molecules, regulatory CD4+T cells limit functional activity of immunocytes and prevent the development of excessive inflammatory reactions and autoimmune diseases. At the same time, there are no available data in literature concerning the sizes of certain functionally active regulatory CD4+T cell subsets in HIV/HCV coinfected patients. Our aim was to estimate the size of functional pool of the regulatory CD4+T lymphocytes in HIV/ HCV coinfected patients receiving antiretroviral therapy.

Two groups of HIV-positive patients were examined: 1) HIV/HCV coinfected subjects (n = 21); 2) HIV mono-infected patients (n = 22). The control group included voluntary blood donors without HIV and HCV infections (n = 23). Regulatory CD4+T lymphocytes were identified by multicolor flow cytometry based on the expression of the following markers: CD3, CD4, CD25, CD127, and FoxP3. Functional subsets of regulatory CD4+T cells were discerned by the expression of CD39, GARP, LAP, and CD71 molecules. Relative and absolute counts of suppressor CD4+T lymphocytes were calculated for each subset. TGF-β1 concentrations in blood plasma were determined with ELISA technique.

Absolute counts of regulatory CD4+T lymphocytes in peripheral blood of HIV/HCV coinfected patients proved to be twice lower than in healthy subjects, while being not accompanied by a decrease in relative frequency of these cells. Despite their deficiency, the number of functionally active CD39-positive,

GARP/LAP-positive, and CD71-positive suppressor cells in HIV/HCV coinfected persons remained at the level found in HIV-monoinfected and healthy people. The frequency of functionally active regulatory CD4+T lymphocytes was increased in HIV/HCV coinfected patients compared with HIV-monoinfected (CD39+, GARP+LAP+) and healthy (CD39+, GARP+LAP+, CD71+) subjects.

In HIV/HCV coinfected patients receiving antiretroviral therapy, the pool of regulatory CD4+T lymphocytes is rich in cells possessing high suppressive capacity. However, the absolute number of functionally active regulatory CD4+T cells remain at the level corresponding to healthy individuals, thus, apparently, is not sufficient to control the systemic inflammation developing in HIV/HCV coinfection.

About the authors

Evgeniya V. Saidakova

Institute of Ecology and Genetic of Microorganisms, Affiliation of Perm Federal Research Center, Ural Branch, Russian Academy of Sciences

Email: radimira@list.ru
ORCID iD: 0000-0002-4342-5362

PhD, MD (Biology), Head, Lavoratory of Molecular Immunology

Russian Federation, 614081, Perm, Goleva str., 3

L. B. Korolevskaya

Institute of Ecology and Genetic of Microorganisms, Affiliation of Perm Federal Research Center, Ural Branch, Russian Academy of Sciences

Email: radimira@list.ru
ORCID iD: 0000-0001-9840-7578

PhD (Medicine), Research Associate, Laboratory of Environmental Immunology

Russian Federation, 614081, Perm, Goleva str., 3

K. V. Shmagel

Institute of Ecology and Genetic of Microorganisms, Affiliation of Perm Federal Research Center, Ural Branch, Russian Academy of Sciences

Author for correspondence.
Email: radimira@list.ru
ORCID iD: 0000-0001-6355-6178

PhD, MD (Medicine), Head, Laboratory of Environmental Immunology

Russian Federation, 614081, Perm, Goleva str., 3

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2. Figure 1. Frequency of CD39-positive regulatory T lymphocytes in HIV/HCV coinfected and HIV monoinfected patients

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3. Figure 2. Frequency of GARP/LAP-positive regulatory T cells and concentrations of TGF-β1 in the peripheral blood of HIV/HCV coinfected and HIV monoinfected patients

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Copyright (c) 2022 Saidakova E.V., Korolevskaya L.B., Shmagel K.V.

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