Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies
Background Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by cha...
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| Veröffentlicht in: | Journal of clinical laboratory analysis 2021-07, Vol.35 (7), p.e23831-n/a |
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| creator | Chen, Hui Ren, ChuanLu Song, HuaFeng Ma, Li‐Ling Chen, Su‐Fang Wu, Min‐Juan Zhang, HuiDan Xu, Jun‐Chi Xu, Ping |
| description | Background
Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required.
Methods
Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation.
Results
The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression.
Conclusions
This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.
At late‐stage (CD4+T cells 500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells 500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We |
| doi_str_mv | 10.1002/jcla.23831 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8275003</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2531533229</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4481-ecb257c1c432e1c99c7b7913600a912c02b0d1319d0ae447e5628e40d3c73b263</originalsourceid><addsrcrecordid>eNp9kc-O0zAQxi0EYruFCw-ALHFBSNkd20njXJCq8meLKnGgcLUcZ5q6pHHWTnbVPfEIvAAvx5PgbJcVcODk0fjnbz7PR8gzBmcMgJ_vTKPPuJCCPSATBoVMuOTZQzIBKfNEAhMn5DSEHQDIgs0ekxORApcgswn5scZ957xuqG4rGjrd21ibrfba9OjtTWy4lroNbbGO9RVSj_XQ6N75A11Tg00TqG3pxfLLz2_fbbvB-K46ny_ffKKjGrZ9oF7bgCFKXNPK6rp1obeG7rX_ij7cTu636HWHw9gPvdc91hbDE_Joo5uAT-_OKfn87u16cZGsPr5fLuarxKSpZAmakme5YSYVHJkpCpOXecHEDEAXjBvgJVRMsKICjWmaYzbjElOohMlFyWdiSl4fdbuh3GNloum4EtV5Gz0elNNW_X3T2q2q3ZWSPM8ARBR4eSfg3eWAoVd7G8bd6BbdEBTPBMuE4LyI6It_0J0bfBu_F6kM0rzIIz0lr46U8S4Ej5t7MwzUmLoaU1e3qUf4-Z_279HfMUeAHYFr2-DhP1Lqw2I1P4r-AnlFu5U</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2550479725</pqid></control><display><type>article</type><title>Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Chen, Hui ; Ren, ChuanLu ; Song, HuaFeng ; Ma, Li‐Ling ; Chen, Su‐Fang ; Wu, Min‐Juan ; Zhang, HuiDan ; Xu, Jun‐Chi ; Xu, Ping</creator><creatorcontrib>Chen, Hui ; Ren, ChuanLu ; Song, HuaFeng ; Ma, Li‐Ling ; Chen, Su‐Fang ; Wu, Min‐Juan ; Zhang, HuiDan ; Xu, Jun‐Chi ; Xu, Ping</creatorcontrib><description>Background
Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required.
Methods
Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation.
Results
The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression.
Conclusions
This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.
At late‐stage (CD4+T cells <200/μl) and intermediate‐stage (CD4+T cells = 200–500/μl), CD4+PD‐1+T were higher than that at early stage (CD4+T cells >500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells <200/μl was higher than those of the groups of CD4+T cells = 200–500/μl and CD4+T cells >500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We also found the percentage of CD4+PD‐1+T had a negative correlation with absolute CD4+ count in the HIV infected/AIDS patients and the percentage of CD4+CD25highTregs was not correlated with absolute CD4+ count. This provides a new quantitative maker for evaluating the progress of immunosuppression.</description><identifier>ISSN: 0887-8013</identifier><identifier>EISSN: 1098-2825</identifier><identifier>DOI: 10.1002/jcla.23831</identifier><identifier>PMID: 34028085</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Acquired immune deficiency syndrome ; Acquired Immunodeficiency Syndrome - diagnosis ; Acquired Immunodeficiency Syndrome - immunology ; Acquired Immunodeficiency Syndrome - therapy ; Adolescent ; Adult ; Aged ; AIDS ; Biomarkers - metabolism ; Blood ; CD25 antigen ; CD3 antigen ; CD4 antigen ; CD4 Antigens - metabolism ; CD4+CD25+Treg ; CD4+PD‐1+T cell ; CD8 antigen ; diagnostic marker ; Down-regulation ; Effector cells ; Female ; Flow cytometry ; Hepatitis B ; Hepatitis C ; HIV ; Human immunodeficiency virus ; Humans ; Immune clearance ; Immune status ; Immune system ; Immunoregulation ; Immunosuppression ; Infections ; Infectious diseases ; Interleukin-2 Receptor alpha Subunit - metabolism ; Lymphocyte Subsets - immunology ; Lymphocytes ; Lymphocytes T ; Male ; Middle Aged ; negative regulatory T cells ; Patients ; T-Lymphocytes, Regulatory - immunology ; Time Factors ; Viruses ; Young Adult</subject><ispartof>Journal of clinical laboratory analysis, 2021-07, Vol.35 (7), p.e23831-n/a</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC</rights><rights>2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). 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-c4481-ecb257c1c432e1c99c7b7913600a912c02b0d1319d0ae447e5628e40d3c73b263</citedby><cites>FETCH-LOGICAL-c4481-ecb257c1c432e1c99c7b7913600a912c02b0d1319d0ae447e5628e40d3c73b263</cites><orcidid>0000-0002-1447-7593 ; 0000-0001-5834-1797</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275003/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275003/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34028085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hui</creatorcontrib><creatorcontrib>Ren, ChuanLu</creatorcontrib><creatorcontrib>Song, HuaFeng</creatorcontrib><creatorcontrib>Ma, Li‐Ling</creatorcontrib><creatorcontrib>Chen, Su‐Fang</creatorcontrib><creatorcontrib>Wu, Min‐Juan</creatorcontrib><creatorcontrib>Zhang, HuiDan</creatorcontrib><creatorcontrib>Xu, Jun‐Chi</creatorcontrib><creatorcontrib>Xu, Ping</creatorcontrib><title>Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies</title><title>Journal of clinical laboratory analysis</title><addtitle>J Clin Lab Anal</addtitle><description>Background
Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required.
Methods
Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation.
Results
The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression.
Conclusions
This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.
At late‐stage (CD4+T cells <200/μl) and intermediate‐stage (CD4+T cells = 200–500/μl), CD4+PD‐1+T were higher than that at early stage (CD4+T cells >500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells <200/μl was higher than those of the groups of CD4+T cells = 200–500/μl and CD4+T cells >500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We also found the percentage of CD4+PD‐1+T had a negative correlation with absolute CD4+ count in the HIV infected/AIDS patients and the percentage of CD4+CD25highTregs was not correlated with absolute CD4+ count. This provides a new quantitative maker for evaluating the progress of immunosuppression.</description><subject>Acquired immune deficiency syndrome</subject><subject>Acquired Immunodeficiency Syndrome - diagnosis</subject><subject>Acquired Immunodeficiency Syndrome - immunology</subject><subject>Acquired Immunodeficiency Syndrome - therapy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>AIDS</subject><subject>Biomarkers - metabolism</subject><subject>Blood</subject><subject>CD25 antigen</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Antigens - metabolism</subject><subject>CD4+CD25+Treg</subject><subject>CD4+PD‐1+T cell</subject><subject>CD8 antigen</subject><subject>diagnostic marker</subject><subject>Down-regulation</subject><subject>Effector cells</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Hepatitis B</subject><subject>Hepatitis C</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune clearance</subject><subject>Immune status</subject><subject>Immune system</subject><subject>Immunoregulation</subject><subject>Immunosuppression</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Lymphocyte Subsets - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>negative regulatory T cells</subject><subject>Patients</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Time Factors</subject><subject>Viruses</subject><subject>Young Adult</subject><issn>0887-8013</issn><issn>1098-2825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc-O0zAQxi0EYruFCw-ALHFBSNkd20njXJCq8meLKnGgcLUcZ5q6pHHWTnbVPfEIvAAvx5PgbJcVcODk0fjnbz7PR8gzBmcMgJ_vTKPPuJCCPSATBoVMuOTZQzIBKfNEAhMn5DSEHQDIgs0ekxORApcgswn5scZ957xuqG4rGjrd21ibrfba9OjtTWy4lroNbbGO9RVSj_XQ6N75A11Tg00TqG3pxfLLz2_fbbvB-K46ny_ffKKjGrZ9oF7bgCFKXNPK6rp1obeG7rX_ij7cTu636HWHw9gPvdc91hbDE_Joo5uAT-_OKfn87u16cZGsPr5fLuarxKSpZAmakme5YSYVHJkpCpOXecHEDEAXjBvgJVRMsKICjWmaYzbjElOohMlFyWdiSl4fdbuh3GNloum4EtV5Gz0elNNW_X3T2q2q3ZWSPM8ARBR4eSfg3eWAoVd7G8bd6BbdEBTPBMuE4LyI6It_0J0bfBu_F6kM0rzIIz0lr46U8S4Ej5t7MwzUmLoaU1e3qUf4-Z_279HfMUeAHYFr2-DhP1Lqw2I1P4r-AnlFu5U</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Chen, Hui</creator><creator>Ren, ChuanLu</creator><creator>Song, HuaFeng</creator><creator>Ma, Li‐Ling</creator><creator>Chen, Su‐Fang</creator><creator>Wu, Min‐Juan</creator><creator>Zhang, HuiDan</creator><creator>Xu, Jun‐Chi</creator><creator>Xu, Ping</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1447-7593</orcidid><orcidid>https://orcid.org/0000-0001-5834-1797</orcidid></search><sort><creationdate>202107</creationdate><title>Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies</title><author>Chen, Hui ; Ren, ChuanLu ; Song, HuaFeng ; Ma, Li‐Ling ; Chen, Su‐Fang ; Wu, Min‐Juan ; Zhang, HuiDan ; Xu, Jun‐Chi ; Xu, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4481-ecb257c1c432e1c99c7b7913600a912c02b0d1319d0ae447e5628e40d3c73b263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Acquired Immunodeficiency Syndrome - diagnosis</topic><topic>Acquired Immunodeficiency Syndrome - immunology</topic><topic>Acquired Immunodeficiency Syndrome - therapy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>AIDS</topic><topic>Biomarkers - metabolism</topic><topic>Blood</topic><topic>CD25 antigen</topic><topic>CD3 antigen</topic><topic>CD4 antigen</topic><topic>CD4 Antigens - metabolism</topic><topic>CD4+CD25+Treg</topic><topic>CD4+PD‐1+T cell</topic><topic>CD8 antigen</topic><topic>diagnostic marker</topic><topic>Down-regulation</topic><topic>Effector cells</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Hepatitis B</topic><topic>Hepatitis C</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune clearance</topic><topic>Immune status</topic><topic>Immune system</topic><topic>Immunoregulation</topic><topic>Immunosuppression</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Lymphocyte Subsets - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>negative regulatory T cells</topic><topic>Patients</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Time Factors</topic><topic>Viruses</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hui</creatorcontrib><creatorcontrib>Ren, ChuanLu</creatorcontrib><creatorcontrib>Song, HuaFeng</creatorcontrib><creatorcontrib>Ma, Li‐Ling</creatorcontrib><creatorcontrib>Chen, Su‐Fang</creatorcontrib><creatorcontrib>Wu, Min‐Juan</creatorcontrib><creatorcontrib>Zhang, HuiDan</creatorcontrib><creatorcontrib>Xu, Jun‐Chi</creatorcontrib><creatorcontrib>Xu, Ping</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical laboratory analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hui</au><au>Ren, ChuanLu</au><au>Song, HuaFeng</au><au>Ma, Li‐Ling</au><au>Chen, Su‐Fang</au><au>Wu, Min‐Juan</au><au>Zhang, HuiDan</au><au>Xu, Jun‐Chi</au><au>Xu, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies</atitle><jtitle>Journal of clinical laboratory analysis</jtitle><addtitle>J Clin Lab Anal</addtitle><date>2021-07</date><risdate>2021</risdate><volume>35</volume><issue>7</issue><spage>e23831</spage><epage>n/a</epage><pages>e23831-n/a</pages><issn>0887-8013</issn><eissn>1098-2825</eissn><abstract>Background
Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required.
Methods
Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation.
Results
The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression.
Conclusions
This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.
At late‐stage (CD4+T cells <200/μl) and intermediate‐stage (CD4+T cells = 200–500/μl), CD4+PD‐1+T were higher than that at early stage (CD4+T cells >500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells <200/μl was higher than those of the groups of CD4+T cells = 200–500/μl and CD4+T cells >500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We also found the percentage of CD4+PD‐1+T had a negative correlation with absolute CD4+ count in the HIV infected/AIDS patients and the percentage of CD4+CD25highTregs was not correlated with absolute CD4+ count. This provides a new quantitative maker for evaluating the progress of immunosuppression.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>34028085</pmid><doi>10.1002/jcla.23831</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-1447-7593</orcidid><orcidid>https://orcid.org/0000-0001-5834-1797</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0887-8013 |
| ispartof | Journal of clinical laboratory analysis, 2021-07, Vol.35 (7), p.e23831-n/a |
| issn | 0887-8013 1098-2825 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8275003 |
| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acquired immune deficiency syndrome Acquired Immunodeficiency Syndrome - diagnosis Acquired Immunodeficiency Syndrome - immunology Acquired Immunodeficiency Syndrome - therapy Adolescent Adult Aged AIDS Biomarkers - metabolism Blood CD25 antigen CD3 antigen CD4 antigen CD4 Antigens - metabolism CD4+CD25+Treg CD4+PD‐1+T cell CD8 antigen diagnostic marker Down-regulation Effector cells Female Flow cytometry Hepatitis B Hepatitis C HIV Human immunodeficiency virus Humans Immune clearance Immune status Immune system Immunoregulation Immunosuppression Infections Infectious diseases Interleukin-2 Receptor alpha Subunit - metabolism Lymphocyte Subsets - immunology Lymphocytes Lymphocytes T Male Middle Aged negative regulatory T cells Patients T-Lymphocytes, Regulatory - immunology Time Factors Viruses Young Adult |
| title | Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T05%3A48%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Temporal%20and%20spatial%20characterization%20of%20negative%20regulatory%20T%20cells%20in%20HIV%E2%80%90infected/AIDS%20patients%20raises%20new%20diagnostic%20markers%20and%20therapeutic%20strategies&rft.jtitle=Journal%20of%20clinical%20laboratory%20analysis&rft.au=Chen,%20Hui&rft.date=2021-07&rft.volume=35&rft.issue=7&rft.spage=e23831&rft.epage=n/a&rft.pages=e23831-n/a&rft.issn=0887-8013&rft.eissn=1098-2825&rft_id=info:doi/10.1002/jcla.23831&rft_dat=%3Cproquest_pubme%3E2531533229%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2550479725&rft_id=info:pmid/34028085&rfr_iscdi=true |