Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes

The activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation to kill infec...

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Main Authors: María José Feito, Mónica Cicuéndez, Laura Casarrubios, Rosalía Diez-Orejas, Sara Fateixa, Daniela Silva, Nathalie Barroca, Paula A. A. P. Marques, María Teresa Portolés
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/18/10625
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author María José Feito
Mónica Cicuéndez
Laura Casarrubios
Rosalía Diez-Orejas
Sara Fateixa
Daniela Silva
Nathalie Barroca
Paula A. A. P. Marques
María Teresa Portolés
author_facet María José Feito
Mónica Cicuéndez
Laura Casarrubios
Rosalía Diez-Orejas
Sara Fateixa
Daniela Silva
Nathalie Barroca
Paula A. A. P. Marques
María Teresa Portolés
author_sort María José Feito
collection DOAJ
description The activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation to kill infected target cells. For these issues, Th lymphocytes must be converted into Th effector cells after their stimulation through their surface receptors TCR/CD3 (by binding to peptide-major histocompatibility complex localized on antigen-presenting cells) and the CD4 co-receptor. After stimulation, Th cells proliferate and differentiate into subpopulations, like Th1, Th2 or Th17, with different functions during the adaptative immune response. Due to the central role of the activation of Th lymphocytes for an accurate adaptative immune response and considering recent preclinical advances in the use of nanomaterials to enhance T-cell therapy, we evaluated in vitro the effects of graphene oxide (GO) and two types of reduced GO (rGO15 and rGO30) nanostructures on the Th2 lymphocyte cell line SR.D10. This cell line offers the possibility of studying their activation threshold by employing soluble antibodies against TCR/CD3 and against CD4, as well as the simultaneous activation of these two receptors. In the present study, the effects of GO, rGO15 and rGO30 on the activation/proliferation rate of these Th2 lymphocytes have been analyzed by studying cell viability, cell cycle phases, intracellular content of reactive oxygen species (ROS) and cytokine secretion. High lymphocyte viability values were obtained after treatment with these nanostructures, as well as increased proliferation in the presence of rGOs. Moreover, rGO15 treatment decreased the intracellular ROS content of Th2 cells in all stimulated conditions. The analysis of these parameters showed that the presence of these GO and rGO nanostructures did not alter the response of Th2 lymphocytes.
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spelling doaj.art-14a0d1ef2aaa4473b4e20612fe272c5c2023-11-23T16:45:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181062510.3390/ijms231810625Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 LymphocytesMaría José Feito0Mónica Cicuéndez1Laura Casarrubios2Rosalía Diez-Orejas3Sara Fateixa4Daniela Silva5Nathalie Barroca6Paula A. A. P. Marques7María Teresa Portolés8Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainDepartamento de Química en Ciencias Farmaceúticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainDepartamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainDepartment of Chemistry and CICECO, University of Aveiro, 3810-193 Aveiro, PortugalCentre for Mechanical Technology & Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, PortugalCentre for Mechanical Technology & Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, PortugalCentre for Mechanical Technology & Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, PortugalDepartamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainThe activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation to kill infected target cells. For these issues, Th lymphocytes must be converted into Th effector cells after their stimulation through their surface receptors TCR/CD3 (by binding to peptide-major histocompatibility complex localized on antigen-presenting cells) and the CD4 co-receptor. After stimulation, Th cells proliferate and differentiate into subpopulations, like Th1, Th2 or Th17, with different functions during the adaptative immune response. Due to the central role of the activation of Th lymphocytes for an accurate adaptative immune response and considering recent preclinical advances in the use of nanomaterials to enhance T-cell therapy, we evaluated in vitro the effects of graphene oxide (GO) and two types of reduced GO (rGO15 and rGO30) nanostructures on the Th2 lymphocyte cell line SR.D10. This cell line offers the possibility of studying their activation threshold by employing soluble antibodies against TCR/CD3 and against CD4, as well as the simultaneous activation of these two receptors. In the present study, the effects of GO, rGO15 and rGO30 on the activation/proliferation rate of these Th2 lymphocytes have been analyzed by studying cell viability, cell cycle phases, intracellular content of reactive oxygen species (ROS) and cytokine secretion. High lymphocyte viability values were obtained after treatment with these nanostructures, as well as increased proliferation in the presence of rGOs. Moreover, rGO15 treatment decreased the intracellular ROS content of Th2 cells in all stimulated conditions. The analysis of these parameters showed that the presence of these GO and rGO nanostructures did not alter the response of Th2 lymphocytes.https://www.mdpi.com/1422-0067/23/18/10625graphene oxidereduced graphene oxidelymphocyteCD4CD3immune response
spellingShingle María José Feito
Mónica Cicuéndez
Laura Casarrubios
Rosalía Diez-Orejas
Sara Fateixa
Daniela Silva
Nathalie Barroca
Paula A. A. P. Marques
María Teresa Portolés
Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
International Journal of Molecular Sciences
graphene oxide
reduced graphene oxide
lymphocyte
CD4
CD3
immune response
title Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
title_full Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
title_fullStr Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
title_full_unstemmed Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
title_short Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4<sup>+</sup> Th2 Lymphocytes
title_sort effects of graphene oxide and reduced graphene oxide nanostructures on cd4 sup sup th2 lymphocytes
topic graphene oxide
reduced graphene oxide
lymphocyte
CD4
CD3
immune response
url https://www.mdpi.com/1422-0067/23/18/10625
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