Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection
•CD31 expression was significantly higher in CD8+ than in CD4 + T cells.•CD31 expression was downregulated in T cells across cellular differentiation stages.•We found higher CD31 expression in memory T-cells of HIV + subjects than in controls.•Memory CD8+ CD31+ population was enriched on PD-1 and ac...
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| Veröffentlicht in: | Immunology letters 2021-07, Vol.235, p.22-31 |
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| creator | Briceño, Olivia Peralta-Prado, Amy Garrido-Rodríguez, Daniela Romero-Mora, Karla Chávez-Torres, Monserrat de la Barrera, Claudia-Alvarado Reyes-Terán, Gustavo Ávila-Ríos, Santiago |
| description | •CD31 expression was significantly higher in CD8+ than in CD4 + T cells.•CD31 expression was downregulated in T cells across cellular differentiation stages.•We found higher CD31 expression in memory T-cells of HIV + subjects than in controls.•Memory CD8+ CD31+ population was enriched on PD-1 and activated cells on HIV infected group.
The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.
We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells.
Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells.
CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0 |
| doi_str_mv | 10.1016/j.imlet.2021.04.004 |
| format | Article |
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The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.
We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells.
Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells.
CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals.
In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.</description><identifier>ISSN: 0165-2478</identifier><identifier>EISSN: 1879-0542</identifier><identifier>DOI: 10.1016/j.imlet.2021.04.004</identifier><identifier>PMID: 33852965</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Biomarkers ; CD38/HLA-DR ; CD4 Lymphocyte Count ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Chronic Disease ; Female ; Gene Expression ; HIV ; HIV Infections - immunology ; HIV Infections - metabolism ; HIV Infections - virology ; HIV-1 - immunology ; Host-Pathogen Interactions - genetics ; Host-Pathogen Interactions - immunology ; Humans ; Immunophenotyping ; Lymphocyte Activation - immunology ; Male ; Memory T Cells - immunology ; Memory T Cells - metabolism ; Middle Aged ; PD-1 ; PECAM-1/CD31 ; Platelet Endothelial Cell Adhesion Molecule-1 - genetics ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism ; T cells ; Viral Load ; Young Adult</subject><ispartof>Immunology letters, 2021-07, Vol.235, p.22-31</ispartof><rights>2021 European Federation of Immunological Societies</rights><rights>Copyright © 2021 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-c1fffbf8b6e5856d9d008acc04bc8e13f52daec8beece180c8cc6a7ce03cb82d3</citedby><cites>FETCH-LOGICAL-c359t-c1fffbf8b6e5856d9d008acc04bc8e13f52daec8beece180c8cc6a7ce03cb82d3</cites><orcidid>0000-0002-6379-9134</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165247821000602$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33852965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Briceño, Olivia</creatorcontrib><creatorcontrib>Peralta-Prado, Amy</creatorcontrib><creatorcontrib>Garrido-Rodríguez, Daniela</creatorcontrib><creatorcontrib>Romero-Mora, Karla</creatorcontrib><creatorcontrib>Chávez-Torres, Monserrat</creatorcontrib><creatorcontrib>de la Barrera, Claudia-Alvarado</creatorcontrib><creatorcontrib>Reyes-Terán, Gustavo</creatorcontrib><creatorcontrib>Ávila-Ríos, Santiago</creatorcontrib><title>Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection</title><title>Immunology letters</title><addtitle>Immunol Lett</addtitle><description>•CD31 expression was significantly higher in CD8+ than in CD4 + T cells.•CD31 expression was downregulated in T cells across cellular differentiation stages.•We found higher CD31 expression in memory T-cells of HIV + subjects than in controls.•Memory CD8+ CD31+ population was enriched on PD-1 and activated cells on HIV infected group.
The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.
We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells.
Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells.
CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals.
In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.</description><subject>Adult</subject><subject>Biomarkers</subject><subject>CD38/HLA-DR</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-CD8 Ratio</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Chronic Disease</subject><subject>Female</subject><subject>Gene Expression</subject><subject>HIV</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - metabolism</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - immunology</subject><subject>Host-Pathogen Interactions - genetics</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Lymphocyte Activation - immunology</subject><subject>Male</subject><subject>Memory T Cells - immunology</subject><subject>Memory T Cells - metabolism</subject><subject>Middle Aged</subject><subject>PD-1</subject><subject>PECAM-1/CD31</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>T cells</subject><subject>Viral Load</subject><subject>Young Adult</subject><issn>0165-2478</issn><issn>1879-0542</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhq0KVBboL6hU5YiEEvyZeA8c0LYUJKReKFfLGY-FV9kktRNE-fU4LO2Rk0fj5_V4HkK-MloxyuqLbRV2HU4Vp5xVVFaUyk9kxXSzLqmS_ICsMqVKLht9RI5T2lLKlJDiMzkSQiu-rtWKdJtHGy1MGMOLncLQF4MvNt8FK_B5jJjS0gp9bsnzwvYuF_r8vgDsuiLN7TiMc_eWSwsFj3HoAxRzP0W0E7ri5vYhX3iEhTklh952Cb-8nyfk9_WP-81Neffr5-3m6q4EodZTCcx733rd1qi0qt3aUaotAJUtaGTCK-4sgm4RAZmmoAFq2wBSAa3mTpyQs_27Yxz-zJgmswtp-bLtcZiT4YoJLkXT0IyKPQpxSCmiN2MMOxv_GkbNotlszZtms2g2VJqsOae-vQ-Y2x26_5l_XjNwuQcwr_kUMJoEAXtAF2J2YdwQPhzwCjSUkIw</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Briceño, Olivia</creator><creator>Peralta-Prado, Amy</creator><creator>Garrido-Rodríguez, Daniela</creator><creator>Romero-Mora, Karla</creator><creator>Chávez-Torres, Monserrat</creator><creator>de la Barrera, Claudia-Alvarado</creator><creator>Reyes-Terán, Gustavo</creator><creator>Ávila-Ríos, Santiago</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0002-6379-9134</orcidid></search><sort><creationdate>202107</creationdate><title>Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection</title><author>Briceño, Olivia ; Peralta-Prado, Amy ; Garrido-Rodríguez, Daniela ; Romero-Mora, Karla ; Chávez-Torres, Monserrat ; de la Barrera, Claudia-Alvarado ; Reyes-Terán, Gustavo ; Ávila-Ríos, Santiago</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-c1fffbf8b6e5856d9d008acc04bc8e13f52daec8beece180c8cc6a7ce03cb82d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Biomarkers</topic><topic>CD38/HLA-DR</topic><topic>CD4 Lymphocyte Count</topic><topic>CD4-CD8 Ratio</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Chronic Disease</topic><topic>Female</topic><topic>Gene Expression</topic><topic>HIV</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - metabolism</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - immunology</topic><topic>Host-Pathogen Interactions - genetics</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Lymphocyte Activation - immunology</topic><topic>Male</topic><topic>Memory T Cells - immunology</topic><topic>Memory T Cells - metabolism</topic><topic>Middle Aged</topic><topic>PD-1</topic><topic>PECAM-1/CD31</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><topic>T cells</topic><topic>Viral Load</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Briceño, Olivia</creatorcontrib><creatorcontrib>Peralta-Prado, Amy</creatorcontrib><creatorcontrib>Garrido-Rodríguez, Daniela</creatorcontrib><creatorcontrib>Romero-Mora, Karla</creatorcontrib><creatorcontrib>Chávez-Torres, Monserrat</creatorcontrib><creatorcontrib>de la Barrera, Claudia-Alvarado</creatorcontrib><creatorcontrib>Reyes-Terán, Gustavo</creatorcontrib><creatorcontrib>Ávila-Ríos, Santiago</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Immunology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Briceño, Olivia</au><au>Peralta-Prado, Amy</au><au>Garrido-Rodríguez, Daniela</au><au>Romero-Mora, Karla</au><au>Chávez-Torres, Monserrat</au><au>de la Barrera, Claudia-Alvarado</au><au>Reyes-Terán, Gustavo</au><au>Ávila-Ríos, Santiago</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection</atitle><jtitle>Immunology letters</jtitle><addtitle>Immunol Lett</addtitle><date>2021-07</date><risdate>2021</risdate><volume>235</volume><spage>22</spage><epage>31</epage><pages>22-31</pages><issn>0165-2478</issn><eissn>1879-0542</eissn><abstract>•CD31 expression was significantly higher in CD8+ than in CD4 + T cells.•CD31 expression was downregulated in T cells across cellular differentiation stages.•We found higher CD31 expression in memory T-cells of HIV + subjects than in controls.•Memory CD8+ CD31+ population was enriched on PD-1 and activated cells on HIV infected group.
The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.
We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells.
Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells.
CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals.
In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33852965</pmid><doi>10.1016/j.imlet.2021.04.004</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-6379-9134</orcidid></addata></record> |
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| ispartof | Immunology letters, 2021-07, Vol.235, p.22-31 |
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| subjects | Adult Biomarkers CD38/HLA-DR CD4 Lymphocyte Count CD4-CD8 Ratio CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Chronic Disease Female Gene Expression HIV HIV Infections - immunology HIV Infections - metabolism HIV Infections - virology HIV-1 - immunology Host-Pathogen Interactions - genetics Host-Pathogen Interactions - immunology Humans Immunophenotyping Lymphocyte Activation - immunology Male Memory T Cells - immunology Memory T Cells - metabolism Middle Aged PD-1 PECAM-1/CD31 Platelet Endothelial Cell Adhesion Molecule-1 - genetics Platelet Endothelial Cell Adhesion Molecule-1 - metabolism T cells Viral Load Young Adult |
| title | Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection |
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