1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset
Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet flu...
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| creator | RIPPA, ALEXANDRA DROTAR, DENISE M. POSGAI, AMANDA HULME, MAIGAN A. WASSERFALL, CLIVE KUSMARTSEVA, IRINA CAMPBELL-THOMPSON, MARTHA ATKINSON, MARK A. |
| description | Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet fluorescent microscopy (LSFM) to quantify CD8+ cells within islets and surrounding exocrine regions.
Methods: Pancreas samples from non-diabetic controls (ND, n = 4; age range 16-24 yr), non-diabetic GAD autoantibody-positive (GADA, n = 3; 18-24 yr), and recent-onset (duration |
| doi_str_mv | 10.2337/db24-1960-LB |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_3100300003</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3100300003</sourcerecordid><originalsourceid>FETCH-LOGICAL-c653-97927294c0c87696470fef7aee935f32aba78c32cb06d785295a84184258f27f3</originalsourceid><addsrcrecordid>eNotkF1LwzAUhoMoOKd3_oADXmo1H23TeLcv3aAwL3bhXUjTBDK3dCYtrP9-HRvn4uXAwwvvg9Azwe-UMf5RVzRNiMhxUk5v0IgIJhJG-e8tGmFMaEK44PfoIcYtxjgfboSOV_wTJsDmMPFq10cXobEwmxevUJrur9F96zSsvHW7NqjWNR6ch2W3Vx4Wvm50cN6A8jUsjtfnR3kdjIqgWtj0BwME5k5VpjUR1j6a9hHdWbWL5umaY7T5Wmxmy6Rcf69mkzLRecYSwQXlVKQa64LnIk85tsZyZYxgmWVUVYoXmlFd4bzmRUZFpoqUFCnNCku5ZWP0cqk9hOa_M7GV26YLw8ooGcGYDSIwG6i3C6VDE2MwVh6C26vQS4LlWa08q5VnV7KcshPkZmir</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3100300003</pqid></control><display><type>article</type><title>1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset</title><source>EZB-FREE-00999 freely available EZB journals</source><creator>RIPPA, ALEXANDRA ; DROTAR, DENISE M. ; POSGAI, AMANDA ; HULME, MAIGAN A. ; WASSERFALL, CLIVE ; KUSMARTSEVA, IRINA ; CAMPBELL-THOMPSON, MARTHA ; ATKINSON, MARK A.</creator><creatorcontrib>RIPPA, ALEXANDRA ; DROTAR, DENISE M. ; POSGAI, AMANDA ; HULME, MAIGAN A. ; WASSERFALL, CLIVE ; KUSMARTSEVA, IRINA ; CAMPBELL-THOMPSON, MARTHA ; ATKINSON, MARK A.</creatorcontrib><description>Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet fluorescent microscopy (LSFM) to quantify CD8+ cells within islets and surrounding exocrine regions.
Methods: Pancreas samples from non-diabetic controls (ND, n = 4; age range 16-24 yr), non-diabetic GAD autoantibody-positive (GADA, n = 3; 18-24 yr), and recent-onset (duration <2 yr) T1D subjects (n = 4; 3-26 yr) were fixed, stained for insulin (INS), glucagon (GCG) and CD8a, cleared and imaged using LSFM. A mean tissue volume of 4.3x108 µm3 per donor was analyzed using Imaris. We generated 3D surfaces (INS+ and GCG+ signals) and 3D spots (CD8a+ cells), with analysis of 516 total islets (201 ND, 162 GADA, 153 T1D). Endocrine pancreas infiltration was quantified using CD8a spots contacting and inside islet surfaces. To assess exocrine infiltration, CD8a spots outside of the islets were quantified. Fold change and mean ± SEM values were analyzed by one-way ANOVA with Tukey's post-test.
Results: T1D donors had significantly increased CD8a+ cells in exocrine (5.5-fold more than ND, 3.6-fold more than GADA, p<0.05) and endocrine pancreas (13-fold more than ND, 12-fold more than GADA, p≤0.02). The percentage of islets containing at least one CD8a+ cell was also increased in T1D (64 ± 0.02%, p<0.05) vs ND (28 ± 0.06%) and GADA (23 ± 0.08%). The maximum number of CD8a+ cells per islet was higher in T1D (133.5 ± 40.5, p≤0.02) vs ND (7.5 ± 2.3) and GADA (10 ± 2.3).
Conclusion: This 3D analysis of the human pancreas provides a comprehensive view of immune cell distribution in T1D, enabling quantification of infiltration throughout the exocrine and endocrine compartments. Such efforts will advance our ability to identify the pathogenic mechanisms underlying pancreatic inflammation in T1D.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db24-1960-LB</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Autoantibodies ; CD8 antigen ; Diabetes ; Diabetes mellitus (insulin dependent) ; Glucagon ; Infiltration ; Inflammation ; Insulitis ; Lymphocytes T ; Pancreas</subject><ispartof>Diabetes (New York, N.Y.), 2024-06, Vol.73 (Supplement_1), p.1</ispartof><rights>Copyright American Diabetes Association Jun 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>RIPPA, ALEXANDRA</creatorcontrib><creatorcontrib>DROTAR, DENISE M.</creatorcontrib><creatorcontrib>POSGAI, AMANDA</creatorcontrib><creatorcontrib>HULME, MAIGAN A.</creatorcontrib><creatorcontrib>WASSERFALL, CLIVE</creatorcontrib><creatorcontrib>KUSMARTSEVA, IRINA</creatorcontrib><creatorcontrib>CAMPBELL-THOMPSON, MARTHA</creatorcontrib><creatorcontrib>ATKINSON, MARK A.</creatorcontrib><title>1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset</title><title>Diabetes (New York, N.Y.)</title><description>Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet fluorescent microscopy (LSFM) to quantify CD8+ cells within islets and surrounding exocrine regions.
Methods: Pancreas samples from non-diabetic controls (ND, n = 4; age range 16-24 yr), non-diabetic GAD autoantibody-positive (GADA, n = 3; 18-24 yr), and recent-onset (duration <2 yr) T1D subjects (n = 4; 3-26 yr) were fixed, stained for insulin (INS), glucagon (GCG) and CD8a, cleared and imaged using LSFM. A mean tissue volume of 4.3x108 µm3 per donor was analyzed using Imaris. We generated 3D surfaces (INS+ and GCG+ signals) and 3D spots (CD8a+ cells), with analysis of 516 total islets (201 ND, 162 GADA, 153 T1D). Endocrine pancreas infiltration was quantified using CD8a spots contacting and inside islet surfaces. To assess exocrine infiltration, CD8a spots outside of the islets were quantified. Fold change and mean ± SEM values were analyzed by one-way ANOVA with Tukey's post-test.
Results: T1D donors had significantly increased CD8a+ cells in exocrine (5.5-fold more than ND, 3.6-fold more than GADA, p<0.05) and endocrine pancreas (13-fold more than ND, 12-fold more than GADA, p≤0.02). The percentage of islets containing at least one CD8a+ cell was also increased in T1D (64 ± 0.02%, p<0.05) vs ND (28 ± 0.06%) and GADA (23 ± 0.08%). The maximum number of CD8a+ cells per islet was higher in T1D (133.5 ± 40.5, p≤0.02) vs ND (7.5 ± 2.3) and GADA (10 ± 2.3).
Conclusion: This 3D analysis of the human pancreas provides a comprehensive view of immune cell distribution in T1D, enabling quantification of infiltration throughout the exocrine and endocrine compartments. Such efforts will advance our ability to identify the pathogenic mechanisms underlying pancreatic inflammation in T1D.</description><subject>Autoantibodies</subject><subject>CD8 antigen</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Glucagon</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Insulitis</subject><subject>Lymphocytes T</subject><subject>Pancreas</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNotkF1LwzAUhoMoOKd3_oADXmo1H23TeLcv3aAwL3bhXUjTBDK3dCYtrP9-HRvn4uXAwwvvg9Azwe-UMf5RVzRNiMhxUk5v0IgIJhJG-e8tGmFMaEK44PfoIcYtxjgfboSOV_wTJsDmMPFq10cXobEwmxevUJrur9F96zSsvHW7NqjWNR6ch2W3Vx4Wvm50cN6A8jUsjtfnR3kdjIqgWtj0BwME5k5VpjUR1j6a9hHdWbWL5umaY7T5Wmxmy6Rcf69mkzLRecYSwQXlVKQa64LnIk85tsZyZYxgmWVUVYoXmlFd4bzmRUZFpoqUFCnNCku5ZWP0cqk9hOa_M7GV26YLw8ooGcGYDSIwG6i3C6VDE2MwVh6C26vQS4LlWa08q5VnV7KcshPkZmir</recordid><startdate>20240614</startdate><enddate>20240614</enddate><creator>RIPPA, ALEXANDRA</creator><creator>DROTAR, DENISE M.</creator><creator>POSGAI, AMANDA</creator><creator>HULME, MAIGAN A.</creator><creator>WASSERFALL, CLIVE</creator><creator>KUSMARTSEVA, IRINA</creator><creator>CAMPBELL-THOMPSON, MARTHA</creator><creator>ATKINSON, MARK A.</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20240614</creationdate><title>1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset</title><author>RIPPA, ALEXANDRA ; DROTAR, DENISE M. ; POSGAI, AMANDA ; HULME, MAIGAN A. ; WASSERFALL, CLIVE ; KUSMARTSEVA, IRINA ; CAMPBELL-THOMPSON, MARTHA ; ATKINSON, MARK A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653-97927294c0c87696470fef7aee935f32aba78c32cb06d785295a84184258f27f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Autoantibodies</topic><topic>CD8 antigen</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Glucagon</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Insulitis</topic><topic>Lymphocytes T</topic><topic>Pancreas</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RIPPA, ALEXANDRA</creatorcontrib><creatorcontrib>DROTAR, DENISE M.</creatorcontrib><creatorcontrib>POSGAI, AMANDA</creatorcontrib><creatorcontrib>HULME, MAIGAN A.</creatorcontrib><creatorcontrib>WASSERFALL, CLIVE</creatorcontrib><creatorcontrib>KUSMARTSEVA, IRINA</creatorcontrib><creatorcontrib>CAMPBELL-THOMPSON, MARTHA</creatorcontrib><creatorcontrib>ATKINSON, MARK A.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RIPPA, ALEXANDRA</au><au>DROTAR, DENISE M.</au><au>POSGAI, AMANDA</au><au>HULME, MAIGAN A.</au><au>WASSERFALL, CLIVE</au><au>KUSMARTSEVA, IRINA</au><au>CAMPBELL-THOMPSON, MARTHA</au><au>ATKINSON, MARK A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2024-06-14</date><risdate>2024</risdate><volume>73</volume><issue>Supplement_1</issue><spage>1</spage><pages>1-</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Introduction: Elevations in immune cell numbers are well documented in both the endocrine and exocrine pancreas in type 1 diabetes (T1D), with CD8+ T cells representing the predominant cell type in islet inflammation (insulitis). To expand on previous 2D characterizations, we used 3D light sheet fluorescent microscopy (LSFM) to quantify CD8+ cells within islets and surrounding exocrine regions.
Methods: Pancreas samples from non-diabetic controls (ND, n = 4; age range 16-24 yr), non-diabetic GAD autoantibody-positive (GADA, n = 3; 18-24 yr), and recent-onset (duration <2 yr) T1D subjects (n = 4; 3-26 yr) were fixed, stained for insulin (INS), glucagon (GCG) and CD8a, cleared and imaged using LSFM. A mean tissue volume of 4.3x108 µm3 per donor was analyzed using Imaris. We generated 3D surfaces (INS+ and GCG+ signals) and 3D spots (CD8a+ cells), with analysis of 516 total islets (201 ND, 162 GADA, 153 T1D). Endocrine pancreas infiltration was quantified using CD8a spots contacting and inside islet surfaces. To assess exocrine infiltration, CD8a spots outside of the islets were quantified. Fold change and mean ± SEM values were analyzed by one-way ANOVA with Tukey's post-test.
Results: T1D donors had significantly increased CD8a+ cells in exocrine (5.5-fold more than ND, 3.6-fold more than GADA, p<0.05) and endocrine pancreas (13-fold more than ND, 12-fold more than GADA, p≤0.02). The percentage of islets containing at least one CD8a+ cell was also increased in T1D (64 ± 0.02%, p<0.05) vs ND (28 ± 0.06%) and GADA (23 ± 0.08%). The maximum number of CD8a+ cells per islet was higher in T1D (133.5 ± 40.5, p≤0.02) vs ND (7.5 ± 2.3) and GADA (10 ± 2.3).
Conclusion: This 3D analysis of the human pancreas provides a comprehensive view of immune cell distribution in T1D, enabling quantification of infiltration throughout the exocrine and endocrine compartments. Such efforts will advance our ability to identify the pathogenic mechanisms underlying pancreatic inflammation in T1D.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db24-1960-LB</doi></addata></record> |
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| subjects | Autoantibodies CD8 antigen Diabetes Diabetes mellitus (insulin dependent) Glucagon Infiltration Inflammation Insulitis Lymphocytes T Pancreas |
| title | 1960-LB: A 3D Analysis of CD8+ Leukocytic Infiltration in Human Endocrine and Exocrine Pancreas at Type 1 Diabetes Onset |
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