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
Hauptverfasser: Young, L.H.Y. (Harvard Medical School, Boston, MA), Peterson, L.B, Wicker, L.S, Persechini, P.M, Young, J.D.E
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container_issue 12
container_start_page 3994
container_title The Journal of immunology (1950)
container_volume 143
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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ispartof The Journal of immunology (1950), 1989-12, Vol.143 (12), p.3994-3999
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language eng
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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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