Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns
Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study...
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description | Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. Increased level of Tc17 and CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase highlights the critical role of IL-17 in RRMS pathogenesis. |
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Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. Increased level of Tc17 and CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase highlights the critical role of IL-17 in RRMS pathogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0159565</identifier><identifier>PMID: 27467597</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Biology ; Biology and life sciences ; Bone morphogenetic proteins ; Brain research ; Care and treatment ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Complications and side effects ; Cytokines ; Cytokines - blood ; Cytometry ; Cytotoxicity ; Enzyme-linked immunosorbent assay ; Female ; Flow cytometry ; Humans ; Immunology ; Influence ; Interferon ; Interleukin 10 ; Interleukin 17 ; Interleukin 21 ; Interleukin 22 ; Interleukin 23 ; Interleukin 4 ; Interleukin 6 ; Laboratories ; Lymphocytes ; Lymphocytes T ; Male ; Medicine and health sciences ; Multiple sclerosis ; Multiple Sclerosis - blood ; Multiple Sclerosis - immunology ; Nervous system ; Neurosciences ; Pathogenesis ; Patients ; Peripheral blood ; Remission ; Studies ; Tumor necrosis factor ; Tumor necrosis factor-α ; γ-Interferon</subject><ispartof>PloS one, 2016-07, Vol.11 (7), p.e0159565-e0159565</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Salehi 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>2016 Salehi et al 2016 Salehi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c795t-e7a12912a36a1911f85199c4f22e20106e38b9a893dba4ed3235fcecc4061c3b3</citedby><cites>FETCH-LOGICAL-c795t-e7a12912a36a1911f85199c4f22e20106e38b9a893dba4ed3235fcecc4061c3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965085/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965085/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27467597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salehi, Zahra</creatorcontrib><creatorcontrib>Doosti, Rozita</creatorcontrib><creatorcontrib>Beheshti, Masoumeh</creatorcontrib><creatorcontrib>Janzamin, Ehsan</creatorcontrib><creatorcontrib>Sahraian, Mohammad Ali</creatorcontrib><creatorcontrib>Izad, Maryam</creatorcontrib><title>Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. 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blood</subject><subject>Multiple Sclerosis - immunology</subject><subject>Nervous system</subject><subject>Neurosciences</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Remission</subject><subject>Studies</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-α</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11vFCEUhidGY2v1HxglaWI0ZlcYhq8bk2ZrtUlNja29JSxzZpfKDiswav-9bHfbdE0vGi4g8Jz3HF44VfWS4DGhgny4DEPsjR8vQw9jTJhinD2qdomi9YjXmD6-s96pnqV0iTGjkvOn1U4tGi6YErvVz0PXdRChz854dBTh1wC9vUKhQ5ND-R6dowl4j86GaYKckOvR18Fnt_SAzqyHGJJL6JvJrigk9MflObow0YUhoYl3vbNFtRxniH16Xj3pjE_wYjPvVT-OPp1PvoxOTj8fTw5ORlYolkcgDKkVqQ3lhihCOsmIUrbp6hpqTDAHKqfKSEXbqWmgpTVlnQVrG8yJpVO6V71e6y59SHrjU9JEYsE4aRQvxPGaaIO51MvoFiZe6WCcvt4IcaZNzK5cUEsADqYRkrXQqFKSkgLaRhDVdlN-rfVxk22YLqC1xYho_Jbo9knv5noWfutSCMOSFYG3G4EYivsp64VLtrhueig-lroJkbJmVD0AxUIqoZQo6P5_6P1GbKiZKXd1fRdKiXYlqg8apqjiDV6lHd9DldHCwtny_zpX9rcC3m0FFCbD3zwzQ0r6-Oz7w9nTi232zR12DsbneQp-yC70aRts1qAtPzRF6G7fg2C9ap8bN_SqffSmfUrYq7tveRt00y_0H-Y9FDY</recordid><startdate>20160728</startdate><enddate>20160728</enddate><creator>Salehi, Zahra</creator><creator>Doosti, Rozita</creator><creator>Beheshti, Masoumeh</creator><creator>Janzamin, Ehsan</creator><creator>Sahraian, Mohammad Ali</creator><creator>Izad, Maryam</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160728</creationdate><title>Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns</title><author>Salehi, Zahra ; Doosti, Rozita ; Beheshti, Masoumeh ; Janzamin, Ehsan ; Sahraian, Mohammad Ali ; Izad, Maryam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c795t-e7a12912a36a1911f85199c4f22e20106e38b9a893dba4ed3235fcecc4061c3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Biology</topic><topic>Biology and life sciences</topic><topic>Bone morphogenetic proteins</topic><topic>Brain research</topic><topic>Care and treatment</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salehi, Zahra</au><au>Doosti, Rozita</au><au>Beheshti, Masoumeh</au><au>Janzamin, Ehsan</au><au>Sahraian, Mohammad Ali</au><au>Izad, Maryam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-07-28</date><risdate>2016</risdate><volume>11</volume><issue>7</issue><spage>e0159565</spage><epage>e0159565</epage><pages>e0159565-e0159565</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. Increased level of Tc17 and CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase highlights the critical role of IL-17 in RRMS pathogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27467597</pmid><doi>10.1371/journal.pone.0159565</doi><tpages>e0159565</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Biology Biology and life sciences Bone morphogenetic proteins Brain research Care and treatment CD8 antigen CD8-Positive T-Lymphocytes - immunology Complications and side effects Cytokines Cytokines - blood Cytometry Cytotoxicity Enzyme-linked immunosorbent assay Female Flow cytometry Humans Immunology Influence Interferon Interleukin 10 Interleukin 17 Interleukin 21 Interleukin 22 Interleukin 23 Interleukin 4 Interleukin 6 Laboratories Lymphocytes Lymphocytes T Male Medicine and health sciences Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - immunology Nervous system Neurosciences Pathogenesis Patients Peripheral blood Remission Studies Tumor necrosis factor Tumor necrosis factor-α γ-Interferon |
title | Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns |
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