In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice
A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may pla...
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Veröffentlicht in: | The Journal of immunology (1950) 1989-12, Vol.143 (12), p.3994-3999 |
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creator | Young, L.H.Y. (Harvard Medical School, Boston, MA) Peterson, L.B Wicker, L.S Persechini, P.M Young, J.D.E |
description | A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease. |
doi_str_mv | 10.4049/jimmunol.143.12.3994 |
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Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Young, L.H.Y. (Harvard Medical School, Boston, MA) ; Peterson, L.B ; Wicker, L.S ; Persechini, P.M ; Young, J.D.E</creator><creatorcontrib>Young, L.H.Y. (Harvard Medical School, Boston, MA) ; Peterson, L.B ; Wicker, L.S ; Persechini, P.M ; Young, J.D.E</creatorcontrib><description>A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.143.12.3994</identifier><identifier>PMID: 2480383</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; ANTIBODIES ; Antibody Specificity ; ANTICORPS ; ANTICUERPOS ; Antigens, Differentiation, T-Lymphocyte ; Autoimmune Diseases - immunology ; Autoimmune Diseases - pathology ; CD8 Antigens ; Cell Movement ; Cells, Cultured ; DIABETE ; DIABETES ; Diabetes Mellitus, Experimental - immunology ; Diabetes Mellitus, Experimental - pathology ; ENFERMEDADES INMUNOLOGICAS ; Immunization, Passive ; IMMUNOLOGICAL DISEASES ; INSULIN ; INSULINA ; INSULINE ; Islets of Langerhans - analysis ; LINFOCITOS ; LYMPHOCYTE ; LYMPHOCYTES ; MALADIE IMMUNOLOGIQUE ; Membrane Glycoproteins ; Membrane Proteins - analysis ; Membrane Proteins - immunology ; MICE ; Mice, Inbred Strains ; Perforin ; Phenotype ; Pore Forming Cytotoxic Proteins ; RATON ; SOURIS ; Staining and Labeling ; T-Lymphocytes, Cytotoxic - analysis ; T-Lymphocytes, Cytotoxic - immunology</subject><ispartof>The Journal of immunology (1950), 1989-12, Vol.143 (12), p.3994-3999</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3814-c6cd8088543691fd934a3b9b6e9eca61f19908ca79486e6c20cb96ee02852cb13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2480383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Young, L.H.Y. (Harvard Medical School, Boston, MA)</creatorcontrib><creatorcontrib>Peterson, L.B</creatorcontrib><creatorcontrib>Wicker, L.S</creatorcontrib><creatorcontrib>Persechini, P.M</creatorcontrib><creatorcontrib>Young, J.D.E</creatorcontrib><title>In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.</description><subject>Animals</subject><subject>ANTIBODIES</subject><subject>Antibody Specificity</subject><subject>ANTICORPS</subject><subject>ANTICUERPOS</subject><subject>Antigens, Differentiation, T-Lymphocyte</subject><subject>Autoimmune Diseases - immunology</subject><subject>Autoimmune Diseases - pathology</subject><subject>CD8 Antigens</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>DIABETE</subject><subject>DIABETES</subject><subject>Diabetes Mellitus, Experimental - immunology</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>ENFERMEDADES INMUNOLOGICAS</subject><subject>Immunization, Passive</subject><subject>IMMUNOLOGICAL DISEASES</subject><subject>INSULIN</subject><subject>INSULINA</subject><subject>INSULINE</subject><subject>Islets of Langerhans - analysis</subject><subject>LINFOCITOS</subject><subject>LYMPHOCYTE</subject><subject>LYMPHOCYTES</subject><subject>MALADIE IMMUNOLOGIQUE</subject><subject>Membrane Glycoproteins</subject><subject>Membrane Proteins - analysis</subject><subject>Membrane Proteins - immunology</subject><subject>MICE</subject><subject>Mice, Inbred Strains</subject><subject>Perforin</subject><subject>Phenotype</subject><subject>Pore Forming Cytotoxic Proteins</subject><subject>RATON</subject><subject>SOURIS</subject><subject>Staining and Labeling</subject><subject>T-Lymphocytes, Cytotoxic - analysis</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV-L1DAUxYMo67j6BUQhTyJIa9Jk0uRRxn8LCz6s-xzS9HYnS5vUpJ2xX8bPatZWwacL95zzu1wOQq8oKTnh6v29G4bZh76knJW0KplS_BHa0f2eFEIQ8RjtCKmqgtaifoqepXRPCBGk4hfoouKSMMl26NeVxyd3Chh-jhFScsHj0OERYhei87hZ8OGjfIf7ZRiPwS4TJJzXZp7Cn_OAW5fAJCjxzTS3LsuZkMbgJ-MhzAkb32LThnFyJ-gXPEXjUwcxQpujpoGN6IMPDSTYls7iwVl4jp50pk_wYpuX6Pbzp--Hr8X1ty9Xhw_XhWWS8sIK20oi5Z4zoWjXKsYNa1QjQIE1gnZUKSKtqRWXAoStiG2UACCV3Fe2oewSvVm5Yww_ZkiTHlyy0PfrE7pWrKakltnIV6ONIaUInR6jG0xcNCX6oRb9txada9G00g-15NjrjT83A7T_QlsPWX-76kd3dzy7CDoNpu-zm-rz-fw_6uVq7UzQ5i66pG9vFKFSkJr9Bs9PpJw</recordid><startdate>19891215</startdate><enddate>19891215</enddate><creator>Young, L.H.Y. (Harvard Medical School, Boston, MA)</creator><creator>Peterson, L.B</creator><creator>Wicker, L.S</creator><creator>Persechini, P.M</creator><creator>Young, J.D.E</creator><general>Am Assoc Immnol</general><scope>FBQ</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>7X8</scope></search><sort><creationdate>19891215</creationdate><title>In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice</title><author>Young, L.H.Y. (Harvard Medical School, Boston, MA) ; Peterson, L.B ; Wicker, L.S ; Persechini, P.M ; Young, J.D.E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3814-c6cd8088543691fd934a3b9b6e9eca61f19908ca79486e6c20cb96ee02852cb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Animals</topic><topic>ANTIBODIES</topic><topic>Antibody Specificity</topic><topic>ANTICORPS</topic><topic>ANTICUERPOS</topic><topic>Antigens, Differentiation, T-Lymphocyte</topic><topic>Autoimmune Diseases - immunology</topic><topic>Autoimmune Diseases - pathology</topic><topic>CD8 Antigens</topic><topic>Cell Movement</topic><topic>Cells, Cultured</topic><topic>DIABETE</topic><topic>DIABETES</topic><topic>Diabetes Mellitus, Experimental - immunology</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>ENFERMEDADES INMUNOLOGICAS</topic><topic>Immunization, Passive</topic><topic>IMMUNOLOGICAL DISEASES</topic><topic>INSULIN</topic><topic>INSULINA</topic><topic>INSULINE</topic><topic>Islets of Langerhans - analysis</topic><topic>LINFOCITOS</topic><topic>LYMPHOCYTE</topic><topic>LYMPHOCYTES</topic><topic>MALADIE IMMUNOLOGIQUE</topic><topic>Membrane Glycoproteins</topic><topic>Membrane Proteins - analysis</topic><topic>Membrane Proteins - immunology</topic><topic>MICE</topic><topic>Mice, Inbred Strains</topic><topic>Perforin</topic><topic>Phenotype</topic><topic>Pore Forming Cytotoxic Proteins</topic><topic>RATON</topic><topic>SOURIS</topic><topic>Staining and Labeling</topic><topic>T-Lymphocytes, Cytotoxic - analysis</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Young, L.H.Y. (Harvard Medical School, Boston, MA)</creatorcontrib><creatorcontrib>Peterson, L.B</creatorcontrib><creatorcontrib>Wicker, L.S</creatorcontrib><creatorcontrib>Persechini, P.M</creatorcontrib><creatorcontrib>Young, J.D.E</creatorcontrib><collection>AGRIS</collection><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>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Young, L.H.Y. (Harvard Medical School, Boston, MA)</au><au>Peterson, L.B</au><au>Wicker, L.S</au><au>Persechini, P.M</au><au>Young, J.D.E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1989-12-15</date><risdate>1989</risdate><volume>143</volume><issue>12</issue><spage>3994</spage><epage>3999</epage><pages>3994-3999</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>2480383</pmid><doi>10.4049/jimmunol.143.12.3994</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals ANTIBODIES Antibody Specificity ANTICORPS ANTICUERPOS Antigens, Differentiation, T-Lymphocyte Autoimmune Diseases - immunology Autoimmune Diseases - pathology CD8 Antigens Cell Movement Cells, Cultured DIABETE DIABETES Diabetes Mellitus, Experimental - immunology Diabetes Mellitus, Experimental - pathology ENFERMEDADES INMUNOLOGICAS Immunization, Passive IMMUNOLOGICAL DISEASES INSULIN INSULINA INSULINE Islets of Langerhans - analysis LINFOCITOS LYMPHOCYTE LYMPHOCYTES MALADIE IMMUNOLOGIQUE Membrane Glycoproteins Membrane Proteins - analysis Membrane Proteins - immunology MICE Mice, Inbred Strains Perforin Phenotype Pore Forming Cytotoxic Proteins RATON SOURIS Staining and Labeling T-Lymphocytes, Cytotoxic - analysis T-Lymphocytes, Cytotoxic - immunology |
title | In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice |
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