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Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens
BACKGROUND. Cytomegalovirus (CMV) immunoglobulin (CMVIG) is used for the prophylaxis of CMV infection after transplantation. Beyond providing passive CMV-specific immunity, CMVIG exerts enhancing and suppressive immunomodulatory functions. Although the anti-inflammatory activities of CMVIG have been...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547921/ https://www.ncbi.nlm.nih.gov/pubmed/34712781 http://dx.doi.org/10.1097/TXD.0000000000001236 |
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author | Deml, Ludwig Hüber, Christian M. Barabas, Sascha Spindler, Theresa Cozzi, Emanuele Grossi, Paolo |
author_facet | Deml, Ludwig Hüber, Christian M. Barabas, Sascha Spindler, Theresa Cozzi, Emanuele Grossi, Paolo |
author_sort | Deml, Ludwig |
collection | PubMed |
description | BACKGROUND. Cytomegalovirus (CMV) immunoglobulin (CMVIG) is used for the prophylaxis of CMV infection after transplantation. Beyond providing passive CMV-specific immunity, CMVIG exerts enhancing and suppressive immunomodulatory functions. Although the anti-inflammatory activities of CMVIG have been extensively documented, its immunostimulatory activities remain poorly characterized. METHODS. This exploratory study analyzed the capacity of CMVIG to modulate cell-mediated innate and adaptive immunities in vitro on freshly isolated peripheral blood mononuclear cells (PBMCs) of CMV-seropositive and -seronegative healthy individuals, using interferon-γ (IFN-γ) enzyme-linked immunospot and intracellular cytokine staining assays. RESULTS. We showed that CMVIG treatment increases the number of IFN-γ–secreting PBMCs of both CMV-seronegative and -seropositive individuals, indicating a global stimulatory effect on innate immune cells. Indeed, CMVIG significantly increased the frequency of natural killer cells producing the T helper cell 1–type cytokines tumor necrosis factor and IFN-γ. This was associated with the induction of interleukin-12–expressing monocytes and the activation of cluster of differentiation (CD) 4(+) and CD8(+) T cells, as measured by the expression of tumor necrosis factor and IFN-γ. Interestingly, stimulation of PBMCs from CMV-seropositive subjects with CMVIG-opsonized CMV antigens (phosphoprotein 65, CMV lysate) enhanced CD4(+) and CD8(+) T-cell activation, suggesting that CMVIG promotes the immunogenicity of CMV antigens. CONCLUSIONS. Our data demonstrate that CMVIG can stimulate effector cells of both innate and adaptive immunities and promote the immunogenicity of CMV antigens. These immunostimulatory properties might contribute to the protective effect against CMV infection mediated by CMVIG. |
format | Online Article Text |
id | pubmed-8547921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-85479212021-10-27 Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens Deml, Ludwig Hüber, Christian M. Barabas, Sascha Spindler, Theresa Cozzi, Emanuele Grossi, Paolo Transplant Direct Infectious Disease BACKGROUND. Cytomegalovirus (CMV) immunoglobulin (CMVIG) is used for the prophylaxis of CMV infection after transplantation. Beyond providing passive CMV-specific immunity, CMVIG exerts enhancing and suppressive immunomodulatory functions. Although the anti-inflammatory activities of CMVIG have been extensively documented, its immunostimulatory activities remain poorly characterized. METHODS. This exploratory study analyzed the capacity of CMVIG to modulate cell-mediated innate and adaptive immunities in vitro on freshly isolated peripheral blood mononuclear cells (PBMCs) of CMV-seropositive and -seronegative healthy individuals, using interferon-γ (IFN-γ) enzyme-linked immunospot and intracellular cytokine staining assays. RESULTS. We showed that CMVIG treatment increases the number of IFN-γ–secreting PBMCs of both CMV-seronegative and -seropositive individuals, indicating a global stimulatory effect on innate immune cells. Indeed, CMVIG significantly increased the frequency of natural killer cells producing the T helper cell 1–type cytokines tumor necrosis factor and IFN-γ. This was associated with the induction of interleukin-12–expressing monocytes and the activation of cluster of differentiation (CD) 4(+) and CD8(+) T cells, as measured by the expression of tumor necrosis factor and IFN-γ. Interestingly, stimulation of PBMCs from CMV-seropositive subjects with CMVIG-opsonized CMV antigens (phosphoprotein 65, CMV lysate) enhanced CD4(+) and CD8(+) T-cell activation, suggesting that CMVIG promotes the immunogenicity of CMV antigens. CONCLUSIONS. Our data demonstrate that CMVIG can stimulate effector cells of both innate and adaptive immunities and promote the immunogenicity of CMV antigens. These immunostimulatory properties might contribute to the protective effect against CMV infection mediated by CMVIG. Lippincott Williams & Wilkins 2021-10-22 /pmc/articles/PMC8547921/ /pubmed/34712781 http://dx.doi.org/10.1097/TXD.0000000000001236 Text en Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Infectious Disease Deml, Ludwig Hüber, Christian M. Barabas, Sascha Spindler, Theresa Cozzi, Emanuele Grossi, Paolo Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title | Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title_full | Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title_fullStr | Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title_full_unstemmed | Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title_short | Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens |
title_sort | stimulatory effect of cmv immunoglobulin on innate immunity and on the immunogenicity of cmv antigens |
topic | Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547921/ https://www.ncbi.nlm.nih.gov/pubmed/34712781 http://dx.doi.org/10.1097/TXD.0000000000001236 |
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