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Hydroxychloroquine reduces T cells activation recall antigen responses
In the context of the current COVID-19 pandemic, there is still limited information about how people suffering from autoimmune diseases respond to the different COVID vaccines. The fact that they are taking an immunosuppressant or other drugs that aim to decrease the immune system activities, such a...
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Published in: | PloS one 2023-08, Vol.18 (8), p.e0287738-e0287738 |
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description | In the context of the current COVID-19 pandemic, there is still limited information about how people suffering from autoimmune diseases respond to the different COVID vaccines. The fact that they are taking an immunosuppressant or other drugs that aim to decrease the immune system activities, such as hydroxychloroquine (HCQ), could also impact their ability to respond to a COVID vaccine and vaccines in general.
Heathy donors were given 200mg of HCQ daily for 6-weeks to assess HCQs impact on the systemic T cells and humoral immune response. Peripheral blood mononuclear cells (PBMC) and plasma were obtained at baseline and 6-weeks after starting daily HCQ. Flow cytometry assays were designed to determine changes in T cell activation and T cell responses. Bead array multiplex were used to analyse antibodies and cytokine levels before and after HCQ intake.
As anticipated, HCQ treatment decreased ex vivo T cell activation. We observed a decrease in CD4+CD161- expressing CCR5 (p = 0.015) and CD69 (p = 0.004) as well as in CD8+CCR5+ (p = 0.003), CD8+CD161+CCR5+ (p = 0.002) and CD8+CD161+CD95+ (p = 0.004). Additionally, HCQ decreased the proportion of Th17 expressing CD29 (p = 0.019), a subset associated with persistent inflammation. The proportion of T regulatory cells expressing the inhibitory molecule TIGIT was also reduced by HCQ (p = 0.003). As well, T cells from people on HCQ were less responsive to activation and cytokine production following stimulation with recall antigens and memory T cells were less likely to produce both IFNγ and TNFα following stimulation.
This study shows HCQ is associated with lower T cell activation and decreased T cell cytokine production. While this study was not performed with the intent of looking at COVID vaccine response, it does provide important information about the changes in immune response that may occur in patient taking HCQ as a treatment for their autoimmune disease. |
doi_str_mv | 10.1371/journal.pone.0287738 |
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Heathy donors were given 200mg of HCQ daily for 6-weeks to assess HCQs impact on the systemic T cells and humoral immune response. Peripheral blood mononuclear cells (PBMC) and plasma were obtained at baseline and 6-weeks after starting daily HCQ. Flow cytometry assays were designed to determine changes in T cell activation and T cell responses. Bead array multiplex were used to analyse antibodies and cytokine levels before and after HCQ intake.
As anticipated, HCQ treatment decreased ex vivo T cell activation. We observed a decrease in CD4+CD161- expressing CCR5 (p = 0.015) and CD69 (p = 0.004) as well as in CD8+CCR5+ (p = 0.003), CD8+CD161+CCR5+ (p = 0.002) and CD8+CD161+CD95+ (p = 0.004). Additionally, HCQ decreased the proportion of Th17 expressing CD29 (p = 0.019), a subset associated with persistent inflammation. The proportion of T regulatory cells expressing the inhibitory molecule TIGIT was also reduced by HCQ (p = 0.003). As well, T cells from people on HCQ were less responsive to activation and cytokine production following stimulation with recall antigens and memory T cells were less likely to produce both IFNγ and TNFα following stimulation.
This study shows HCQ is associated with lower T cell activation and decreased T cell cytokine production. While this study was not performed with the intent of looking at COVID vaccine response, it does provide important information about the changes in immune response that may occur in patient taking HCQ as a treatment for their autoimmune disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0287738</identifier><identifier>PMID: 37531383</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies ; Antigens ; Autoimmune diseases ; Biology and Life Sciences ; CC chemokine receptors ; CD29 antigen ; CD4 antigen ; CD69 antigen ; CD8 antigen ; CD95 antigen ; Cell activation ; COVID-19 ; COVID-19 Drug Treatment ; COVID-19 Vaccines ; Cytokines ; Disease ; Drug dosages ; Flow cytometry ; Health aspects ; Health services ; Helper cells ; HIV ; Human immunodeficiency virus ; Humans ; Hydroxychloroquine ; Hydroxychloroquine - pharmacology ; Hydroxychloroquine - therapeutic use ; Immune response ; Immune response (humoral) ; Immune system ; Immunological memory ; Immunoregulation ; Immunosuppressive agents ; Influenza ; Leukocytes, Mononuclear ; Lupus ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Memory cells ; Pandemics ; Peptides ; Peripheral blood mononuclear cells ; Properties ; Recall ; Rheumatoid arthritis ; Severe acute respiratory syndrome coronavirus 2 ; Stimulation ; T cells ; Tumor Necrosis Factor Receptor Superfamily, Member 7 ; Tumor necrosis factor-TNF ; Vaccines ; Vagina ; Viral antibodies ; Womens health ; γ-Interferon</subject><ispartof>PloS one, 2023-08, Vol.18 (8), p.e0287738-e0287738</ispartof><rights>Copyright: © 2023 Kowatsch et al. 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.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Kowatsch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Kowatsch et al 2023 Kowatsch et al</rights><rights>2023 Kowatsch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c627t-ed36c6cf21f6c293f103bd9b76030c605b357ce7bc02cd3ca7da2fb31b5cda6a3</citedby><cites>FETCH-LOGICAL-c627t-ed36c6cf21f6c293f103bd9b76030c605b357ce7bc02cd3ca7da2fb31b5cda6a3</cites><orcidid>0000-0001-8227-6649</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2845067207/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2845067207?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,38516,43895,44590,53791,53793,74412,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37531383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Nouhin, Janin</contributor><creatorcontrib>Kowatsch, Monika M</creatorcontrib><creatorcontrib>Lajoie, Julie</creatorcontrib><creatorcontrib>Mwangi, Lucy</creatorcontrib><creatorcontrib>Omollo, Kenneth</creatorcontrib><creatorcontrib>Oyugi, Julius</creatorcontrib><creatorcontrib>Hollett, Natasha</creatorcontrib><creatorcontrib>Kimani, Joshua</creatorcontrib><creatorcontrib>Fowke, Keith R</creatorcontrib><title>Hydroxychloroquine reduces T cells activation recall antigen responses</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In the context of the current COVID-19 pandemic, there is still limited information about how people suffering from autoimmune diseases respond to the different COVID vaccines. The fact that they are taking an immunosuppressant or other drugs that aim to decrease the immune system activities, such as hydroxychloroquine (HCQ), could also impact their ability to respond to a COVID vaccine and vaccines in general.
Heathy donors were given 200mg of HCQ daily for 6-weeks to assess HCQs impact on the systemic T cells and humoral immune response. Peripheral blood mononuclear cells (PBMC) and plasma were obtained at baseline and 6-weeks after starting daily HCQ. Flow cytometry assays were designed to determine changes in T cell activation and T cell responses. Bead array multiplex were used to analyse antibodies and cytokine levels before and after HCQ intake.
As anticipated, HCQ treatment decreased ex vivo T cell activation. We observed a decrease in CD4+CD161- expressing CCR5 (p = 0.015) and CD69 (p = 0.004) as well as in CD8+CCR5+ (p = 0.003), CD8+CD161+CCR5+ (p = 0.002) and CD8+CD161+CD95+ (p = 0.004). Additionally, HCQ decreased the proportion of Th17 expressing CD29 (p = 0.019), a subset associated with persistent inflammation. The proportion of T regulatory cells expressing the inhibitory molecule TIGIT was also reduced by HCQ (p = 0.003). As well, T cells from people on HCQ were less responsive to activation and cytokine production following stimulation with recall antigens and memory T cells were less likely to produce both IFNγ and TNFα following stimulation.
This study shows HCQ is associated with lower T cell activation and decreased T cell cytokine production. While this study was not performed with the intent of looking at COVID vaccine response, it does provide important information about the changes in immune response that may occur in patient taking HCQ as a treatment for their autoimmune disease.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Autoimmune diseases</subject><subject>Biology and Life Sciences</subject><subject>CC chemokine receptors</subject><subject>CD29 antigen</subject><subject>CD4 antigen</subject><subject>CD69 antigen</subject><subject>CD8 antigen</subject><subject>CD95 antigen</subject><subject>Cell activation</subject><subject>COVID-19</subject><subject>COVID-19 Drug Treatment</subject><subject>COVID-19 Vaccines</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Drug dosages</subject><subject>Flow cytometry</subject><subject>Health aspects</subject><subject>Health services</subject><subject>Helper cells</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hydroxychloroquine</subject><subject>Hydroxychloroquine - pharmacology</subject><subject>Hydroxychloroquine - therapeutic use</subject><subject>Immune response</subject><subject>Immune response (humoral)</subject><subject>Immune system</subject><subject>Immunological memory</subject><subject>Immunoregulation</subject><subject>Immunosuppressive agents</subject><subject>Influenza</subject><subject>Leukocytes, Mononuclear</subject><subject>Lupus</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine and Health Sciences</subject><subject>Memory cells</subject><subject>Pandemics</subject><subject>Peptides</subject><subject>Peripheral blood mononuclear cells</subject><subject>Properties</subject><subject>Recall</subject><subject>Rheumatoid arthritis</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Stimulation</subject><subject>T cells</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 7</subject><subject>Tumor necrosis factor-TNF</subject><subject>Vaccines</subject><subject>Vagina</subject><subject>Viral antibodies</subject><subject>Womens 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reduces T cells activation recall antigen responses</title><author>Kowatsch, Monika M ; Lajoie, Julie ; Mwangi, Lucy ; Omollo, Kenneth ; Oyugi, Julius ; Hollett, Natasha ; Kimani, Joshua ; Fowke, Keith R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c627t-ed36c6cf21f6c293f103bd9b76030c605b357ce7bc02cd3ca7da2fb31b5cda6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antibodies</topic><topic>Antigens</topic><topic>Autoimmune diseases</topic><topic>Biology and Life Sciences</topic><topic>CC chemokine receptors</topic><topic>CD29 antigen</topic><topic>CD4 antigen</topic><topic>CD69 antigen</topic><topic>CD8 antigen</topic><topic>CD95 antigen</topic><topic>Cell activation</topic><topic>COVID-19</topic><topic>COVID-19 Drug Treatment</topic><topic>COVID-19 Vaccines</topic><topic>Cytokines</topic><topic>Disease</topic><topic>Drug dosages</topic><topic>Flow 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One</addtitle><date>2023-08-02</date><risdate>2023</risdate><volume>18</volume><issue>8</issue><spage>e0287738</spage><epage>e0287738</epage><pages>e0287738-e0287738</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In the context of the current COVID-19 pandemic, there is still limited information about how people suffering from autoimmune diseases respond to the different COVID vaccines. The fact that they are taking an immunosuppressant or other drugs that aim to decrease the immune system activities, such as hydroxychloroquine (HCQ), could also impact their ability to respond to a COVID vaccine and vaccines in general.
Heathy donors were given 200mg of HCQ daily for 6-weeks to assess HCQs impact on the systemic T cells and humoral immune response. Peripheral blood mononuclear cells (PBMC) and plasma were obtained at baseline and 6-weeks after starting daily HCQ. Flow cytometry assays were designed to determine changes in T cell activation and T cell responses. Bead array multiplex were used to analyse antibodies and cytokine levels before and after HCQ intake.
As anticipated, HCQ treatment decreased ex vivo T cell activation. We observed a decrease in CD4+CD161- expressing CCR5 (p = 0.015) and CD69 (p = 0.004) as well as in CD8+CCR5+ (p = 0.003), CD8+CD161+CCR5+ (p = 0.002) and CD8+CD161+CD95+ (p = 0.004). Additionally, HCQ decreased the proportion of Th17 expressing CD29 (p = 0.019), a subset associated with persistent inflammation. The proportion of T regulatory cells expressing the inhibitory molecule TIGIT was also reduced by HCQ (p = 0.003). As well, T cells from people on HCQ were less responsive to activation and cytokine production following stimulation with recall antigens and memory T cells were less likely to produce both IFNγ and TNFα following stimulation.
This study shows HCQ is associated with lower T cell activation and decreased T cell cytokine production. While this study was not performed with the intent of looking at COVID vaccine response, it does provide important information about the changes in immune response that may occur in patient taking HCQ as a treatment for their autoimmune disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37531383</pmid><doi>10.1371/journal.pone.0287738</doi><tpages>e0287738</tpages><orcidid>https://orcid.org/0000-0001-8227-6649</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2023-08, Vol.18 (8), p.e0287738-e0287738 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2845067207 |
source | PubMed Central Free; Publicly Available Content Database; Coronavirus Research Database |
subjects | Antibodies Antigens Autoimmune diseases Biology and Life Sciences CC chemokine receptors CD29 antigen CD4 antigen CD69 antigen CD8 antigen CD95 antigen Cell activation COVID-19 COVID-19 Drug Treatment COVID-19 Vaccines Cytokines Disease Drug dosages Flow cytometry Health aspects Health services Helper cells HIV Human immunodeficiency virus Humans Hydroxychloroquine Hydroxychloroquine - pharmacology Hydroxychloroquine - therapeutic use Immune response Immune response (humoral) Immune system Immunological memory Immunoregulation Immunosuppressive agents Influenza Leukocytes, Mononuclear Lupus Lymphocytes Lymphocytes T Medicine and Health Sciences Memory cells Pandemics Peptides Peripheral blood mononuclear cells Properties Recall Rheumatoid arthritis Severe acute respiratory syndrome coronavirus 2 Stimulation T cells Tumor Necrosis Factor Receptor Superfamily, Member 7 Tumor necrosis factor-TNF Vaccines Vagina Viral antibodies Womens health γ-Interferon |
title | Hydroxychloroquine reduces T cells activation recall antigen responses |
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