Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype
Aims/hypothesis The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. Methods Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with n...
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| Veröffentlicht in: | Diabetologia 2020-06, Vol.63 (6), p.1174-1185 |
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| creator | Hanna, Stephanie J. Powell, Wendy E. Long, Anna E. Robinson, Emma J. S. Davies, Joanne Megson, Clare Howell, Alexandra Jones, Taz J. Ladell, Kristin Price, David A. Dayan, Colin M. Williams, Alistair J. K. Gillespie, Kathleen M. Wong, F. Susan |
| description | Aims/hypothesis
The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes.
Methods
Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8
+
T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs.
Results
Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (
p
|
| doi_str_mv | 10.1007/s00125-020-05114-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7228996</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2376228864</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2967-743ca7a96b02995c3491fe19b6470d49db14f239dfb5c96c5a9ce8a8c6423d643</originalsourceid><addsrcrecordid>eNp9ks1u1DAUhS0EotPCC7CyxAaJBvwXO94gleFXqsSCIrGzHOdmxlUmDrYzpe_Dg-LMFBAsWN3F-c6590oHoSeUvKCEqJeJEMrqijBSkZpSUal7aEUFZxURrLmPVote0UZ-PUGnKV0TQngt5EN0whmtFedshX58HsINnmLYREgpxIRzwPl2Akxx520LGRIeQgLs0wAZ2zkHO2bfhs4XJewh4ux3cI63dg-4h5tfYIE2MFZpAud77_D6TfMcX2EHw5CK2mH4vvWtL2RZlLIfXS6Mrrcevz5QeNrCGJZbHqEHvR0SPL6bZ-jLu7dX6w_V5af3H9cXl5VjWqpKCe6sslq2hGldOy407YHqVgpFOqG7loqecd31be20dLXVDhrbOCkY76TgZ-jVMXea2x10DsYc7WCm6Hc23ppgvflbGf3WbMLeKMYarWUJeHYXEMO3GVI2O5-WX-wIYU6GcSUL2hx2Pf0HvQ5zHMt7hgnCmeC8WSh2pFwMKUXofx9DiVlKYI4lMKUE5lACo4qJH02pwOMG4p_o_7h-AvxVtJM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2403243384</pqid></control><display><type>article</type><title>Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype</title><source>SpringerLink Journals - AutoHoldings</source><creator>Hanna, Stephanie J. ; Powell, Wendy E. ; Long, Anna E. ; Robinson, Emma J. S. ; Davies, Joanne ; Megson, Clare ; Howell, Alexandra ; Jones, Taz J. ; Ladell, Kristin ; Price, David A. ; Dayan, Colin M. ; Williams, Alistair J. K. ; Gillespie, Kathleen M. ; Wong, F. Susan</creator><creatorcontrib>Hanna, Stephanie J. ; Powell, Wendy E. ; Long, Anna E. ; Robinson, Emma J. S. ; Davies, Joanne ; Megson, Clare ; Howell, Alexandra ; Jones, Taz J. ; Ladell, Kristin ; Price, David A. ; Dayan, Colin M. ; Williams, Alistair J. K. ; Gillespie, Kathleen M. ; Wong, F. Susan</creatorcontrib><description>Aims/hypothesis
The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes.
Methods
Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8
+
T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs.
Results
Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (
p
< 0.05). The phenotypic characteristics of CD4
+
and CD8
+
T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4
+
T cells with a central memory phenotype (CD27
int
, CD127
+
, CD95
int
) were observed in slow progressors compared with healthy donors (mean percentage of total CD4
+
T cells was 3.00% in slow progressors vs 4.67% in healthy donors,
p
< 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors,
p
< 0.05) in an ELISpot assay. Islet autoantigen-specific CD8
+
T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors,
p
= 0.06).
Conclusions/interpretation
In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05114-7</identifier><identifier>PMID: 32157332</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Apoptosis ; Autoantibodies ; Beta cells ; CD4 antigen ; CD8 antigen ; CD95 antigen ; Chemokines ; Diabetes ; Diabetes mellitus (insulin dependent) ; Enzyme-linked immunosorbent assay ; FasL protein ; Flow cytometry ; Genotype & phenotype ; Histocompatibility antigen HLA ; Human Physiology ; Insulin ; Internal Medicine ; Lymphocytes ; Lymphocytes T ; Medicine ; Medicine & Public Health ; Memory cells ; Metabolic Diseases ; Peripheral blood ; Phenotypes ; Serum levels</subject><ispartof>Diabetologia, 2020-06, Vol.63 (6), p.1174-1185</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/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-c2967-743ca7a96b02995c3491fe19b6470d49db14f239dfb5c96c5a9ce8a8c6423d643</citedby><cites>FETCH-LOGICAL-c2967-743ca7a96b02995c3491fe19b6470d49db14f239dfb5c96c5a9ce8a8c6423d643</cites><orcidid>0000-0002-0821-4498</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05114-7$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05114-7$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,778,782,883,27911,27912,41475,42544,51306</link.rule.ids></links><search><creatorcontrib>Hanna, Stephanie J.</creatorcontrib><creatorcontrib>Powell, Wendy E.</creatorcontrib><creatorcontrib>Long, Anna E.</creatorcontrib><creatorcontrib>Robinson, Emma J. S.</creatorcontrib><creatorcontrib>Davies, Joanne</creatorcontrib><creatorcontrib>Megson, Clare</creatorcontrib><creatorcontrib>Howell, Alexandra</creatorcontrib><creatorcontrib>Jones, Taz J.</creatorcontrib><creatorcontrib>Ladell, Kristin</creatorcontrib><creatorcontrib>Price, David A.</creatorcontrib><creatorcontrib>Dayan, Colin M.</creatorcontrib><creatorcontrib>Williams, Alistair J. K.</creatorcontrib><creatorcontrib>Gillespie, Kathleen M.</creatorcontrib><creatorcontrib>Wong, F. Susan</creatorcontrib><title>Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes.
Methods
Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8
+
T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs.
Results
Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (
p
< 0.05). The phenotypic characteristics of CD4
+
and CD8
+
T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4
+
T cells with a central memory phenotype (CD27
int
, CD127
+
, CD95
int
) were observed in slow progressors compared with healthy donors (mean percentage of total CD4
+
T cells was 3.00% in slow progressors vs 4.67% in healthy donors,
p
< 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors,
p
< 0.05) in an ELISpot assay. Islet autoantigen-specific CD8
+
T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors,
p
= 0.06).
Conclusions/interpretation
In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications.</description><subject>Apoptosis</subject><subject>Autoantibodies</subject><subject>Beta cells</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD95 antigen</subject><subject>Chemokines</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>FasL protein</subject><subject>Flow cytometry</subject><subject>Genotype & phenotype</subject><subject>Histocompatibility antigen HLA</subject><subject>Human Physiology</subject><subject>Insulin</subject><subject>Internal Medicine</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Memory cells</subject><subject>Metabolic Diseases</subject><subject>Peripheral blood</subject><subject>Phenotypes</subject><subject>Serum levels</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9ks1u1DAUhS0EotPCC7CyxAaJBvwXO94gleFXqsSCIrGzHOdmxlUmDrYzpe_Dg-LMFBAsWN3F-c6590oHoSeUvKCEqJeJEMrqijBSkZpSUal7aEUFZxURrLmPVote0UZ-PUGnKV0TQngt5EN0whmtFedshX58HsINnmLYREgpxIRzwPl2Akxx520LGRIeQgLs0wAZ2zkHO2bfhs4XJewh4ux3cI63dg-4h5tfYIE2MFZpAud77_D6TfMcX2EHw5CK2mH4vvWtL2RZlLIfXS6Mrrcevz5QeNrCGJZbHqEHvR0SPL6bZ-jLu7dX6w_V5af3H9cXl5VjWqpKCe6sslq2hGldOy407YHqVgpFOqG7loqecd31be20dLXVDhrbOCkY76TgZ-jVMXea2x10DsYc7WCm6Hc23ppgvflbGf3WbMLeKMYarWUJeHYXEMO3GVI2O5-WX-wIYU6GcSUL2hx2Pf0HvQ5zHMt7hgnCmeC8WSh2pFwMKUXofx9DiVlKYI4lMKUE5lACo4qJH02pwOMG4p_o_7h-AvxVtJM</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Hanna, Stephanie J.</creator><creator>Powell, Wendy E.</creator><creator>Long, Anna E.</creator><creator>Robinson, Emma J. S.</creator><creator>Davies, Joanne</creator><creator>Megson, Clare</creator><creator>Howell, Alexandra</creator><creator>Jones, Taz J.</creator><creator>Ladell, Kristin</creator><creator>Price, David A.</creator><creator>Dayan, Colin M.</creator><creator>Williams, Alistair J. K.</creator><creator>Gillespie, Kathleen M.</creator><creator>Wong, F. Susan</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0821-4498</orcidid></search><sort><creationdate>20200601</creationdate><title>Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype</title><author>Hanna, Stephanie J. ; Powell, Wendy E. ; Long, Anna E. ; Robinson, Emma J. S. ; Davies, Joanne ; Megson, Clare ; Howell, Alexandra ; Jones, Taz J. ; Ladell, Kristin ; Price, David A. ; Dayan, Colin M. ; Williams, Alistair J. K. ; Gillespie, Kathleen M. ; Wong, F. Susan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2967-743ca7a96b02995c3491fe19b6470d49db14f239dfb5c96c5a9ce8a8c6423d643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Autoantibodies</topic><topic>Beta cells</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>CD95 antigen</topic><topic>Chemokines</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>FasL protein</topic><topic>Flow cytometry</topic><topic>Genotype & phenotype</topic><topic>Histocompatibility antigen HLA</topic><topic>Human Physiology</topic><topic>Insulin</topic><topic>Internal Medicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Memory cells</topic><topic>Metabolic Diseases</topic><topic>Peripheral blood</topic><topic>Phenotypes</topic><topic>Serum levels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanna, Stephanie J.</creatorcontrib><creatorcontrib>Powell, Wendy E.</creatorcontrib><creatorcontrib>Long, Anna E.</creatorcontrib><creatorcontrib>Robinson, Emma J. S.</creatorcontrib><creatorcontrib>Davies, Joanne</creatorcontrib><creatorcontrib>Megson, Clare</creatorcontrib><creatorcontrib>Howell, Alexandra</creatorcontrib><creatorcontrib>Jones, Taz J.</creatorcontrib><creatorcontrib>Ladell, Kristin</creatorcontrib><creatorcontrib>Price, David A.</creatorcontrib><creatorcontrib>Dayan, Colin M.</creatorcontrib><creatorcontrib>Williams, Alistair J. K.</creatorcontrib><creatorcontrib>Gillespie, Kathleen M.</creatorcontrib><creatorcontrib>Wong, F. Susan</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanna, Stephanie J.</au><au>Powell, Wendy E.</au><au>Long, Anna E.</au><au>Robinson, Emma J. S.</au><au>Davies, Joanne</au><au>Megson, Clare</au><au>Howell, Alexandra</au><au>Jones, Taz J.</au><au>Ladell, Kristin</au><au>Price, David A.</au><au>Dayan, Colin M.</au><au>Williams, Alistair J. K.</au><au>Gillespie, Kathleen M.</au><au>Wong, F. Susan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><date>2020-06-01</date><risdate>2020</risdate><volume>63</volume><issue>6</issue><spage>1174</spage><epage>1185</epage><pages>1174-1185</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes.
Methods
Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8
+
T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs.
Results
Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (
p
< 0.05). The phenotypic characteristics of CD4
+
and CD8
+
T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4
+
T cells with a central memory phenotype (CD27
int
, CD127
+
, CD95
int
) were observed in slow progressors compared with healthy donors (mean percentage of total CD4
+
T cells was 3.00% in slow progressors vs 4.67% in healthy donors,
p
< 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors,
p
< 0.05) in an ELISpot assay. Islet autoantigen-specific CD8
+
T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors,
p
= 0.06).
Conclusions/interpretation
In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32157332</pmid><doi>10.1007/s00125-020-05114-7</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-0821-4498</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2020-06, Vol.63 (6), p.1174-1185 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7228996 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Apoptosis Autoantibodies Beta cells CD4 antigen CD8 antigen CD95 antigen Chemokines Diabetes Diabetes mellitus (insulin dependent) Enzyme-linked immunosorbent assay FasL protein Flow cytometry Genotype & phenotype Histocompatibility antigen HLA Human Physiology Insulin Internal Medicine Lymphocytes Lymphocytes T Medicine Medicine & Public Health Memory cells Metabolic Diseases Peripheral blood Phenotypes Serum levels |
| title | Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype |
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