Publicação
Breakpoints in immunoregulation required for Th1 cells to induce diabetes
| Resumo: | We describe a novel TCR-transgenic mouse line, TCR7, where MHC class II-restricted, CD4+ T cells are specific for the subdominant H-2b epitope (HEL74-88) of hen egg lysozyme (HEL), and displayed an increased frequency in the thymus and in peripheral lymphoid compartments over that seen in non-transgenic littermate controls. CD4+ T cells responded vigorously to HEL or HEL74-88 epitope presented on APC and could develop into Th1 or Th2 cells under appropriate conditions. Adoptive transfer of TCR7 Ly5.1 T cells into Ly5.2 rat insulin promoter (RIP)-HEL transgenic recipient hosts did not lead to expansion of these cells or result in islet infiltration, although these TCR7 cells could expand upon transfer into mice expressing high levels of HEL in the serum. Islet cell infiltration only occurred when the TCR7 cells had been polarized to either a Th1 or Th2 phenotype prior to transfer, which led to insulitis. Progression from insulitis to autoimmune diabetes only occurred in these recipients when Th1 but not Th2 TCR7 cells were transferred and CTLA-4 signaling was simultaneously blocked. These findings show that regulatory pathways such as CTLA-4 can hold in check already differentiated autoreactive effector Th1 cells, to inhibit the transition from tolerance to autoimmune diabetes. |
|---|---|
| Autores principais: | Neighbors, Margaret |
| Outros Autores: | Hartley, Suzanne B.; Xu, Xiuling; Castro, António G.; Bouley, Donna M.; O'Garra, Anne |
| Assunto: | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| Ano: | 2006 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867437999629795328 |
|---|---|
| author | Neighbors, Margaret |
| author2 | Hartley, Suzanne B. Xu, Xiuling Castro, António G. Bouley, Donna M. O'Garra, Anne |
| author2_role | author author author author author |
| author_facet | Neighbors, Margaret Hartley, Suzanne B. Xu, Xiuling Castro, António G. Bouley, Donna M. O'Garra, Anne |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Neighbors, Margaret\"},{\"Person.name\":\"Hartley, Suzanne B.\"},{\"Person.name\":\"Xu, Xiuling\"},{\"Person.name\":\"Castro, António G.\"},{\"Person.name\":\"Bouley, Donna M.\"},{\"Person.name\":\"O'Garra, Anne\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Neighbors, Margaret Hartley, Suzanne B. Xu, Xiuling Castro, António G. Bouley, Donna M. O'Garra, Anne |
| datacite.date.Accepted.fl_str_mv | 2006-09-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-10-30T15:32:18Z |
| datacite.date.embargoed.fl_str_mv | 2020-10-30T15:32:18Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| datacite.titles.title.fl_str_mv | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Neighbors, Margaret Hartley, Suzanne B. Xu, Xiuling Castro, António G. Bouley, Donna M. O'Garra, Anne |
| dc.date.Accepted.fl_str_mv | 2006-09-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-10-30T15:32:18Z |
| dc.date.embargoed.fl_str_mv | 2020-10-30T15:32:18Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/67936 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Wiley |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| dc.title.fl_str_mv | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | We describe a novel TCR-transgenic mouse line, TCR7, where MHC class II-restricted, CD4+ T cells are specific for the subdominant H-2b epitope (HEL74-88) of hen egg lysozyme (HEL), and displayed an increased frequency in the thymus and in peripheral lymphoid compartments over that seen in non-transgenic littermate controls. CD4+ T cells responded vigorously to HEL or HEL74-88 epitope presented on APC and could develop into Th1 or Th2 cells under appropriate conditions. Adoptive transfer of TCR7 Ly5.1 T cells into Ly5.2 rat insulin promoter (RIP)-HEL transgenic recipient hosts did not lead to expansion of these cells or result in islet infiltration, although these TCR7 cells could expand upon transfer into mice expressing high levels of HEL in the serum. Islet cell infiltration only occurred when the TCR7 cells had been polarized to either a Th1 or Th2 phenotype prior to transfer, which led to insulitis. Progression from insulitis to autoimmune diabetes only occurred in these recipients when Th1 but not Th2 TCR7 cells were transferred and CTLA-4 signaling was simultaneously blocked. These findings show that regulatory pathways such as CTLA-4 can hold in check already differentiated autoreactive effector Th1 cells, to inhibit the transition from tolerance to autoimmune diabetes. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/9973ea6b-b8d7-4ce1-ada9-7caa1ec1a496/download |
| id | rum_fa6e2ef8e9d6ff4f56c1abd64f356721 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/67936 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/67936 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Neighbors, Margaret Hartley, Suzanne B. Xu, Xiuling Castro, António G. Bouley, Donna M. O'Garra, Anne |
| publishDate | 2006 |
| publisher.none.fl_str_mv | Wiley |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engWileyporWe describe a novel TCR-transgenic mouse line, TCR7, where MHC class II-restricted, CD4+ T cells are specific for the subdominant H-2b epitope (HEL74-88) of hen egg lysozyme (HEL), and displayed an increased frequency in the thymus and in peripheral lymphoid compartments over that seen in non-transgenic littermate controls. CD4+ T cells responded vigorously to HEL or HEL74-88 epitope presented on APC and could develop into Th1 or Th2 cells under appropriate conditions. Adoptive transfer of TCR7 Ly5.1 T cells into Ly5.2 rat insulin promoter (RIP)-HEL transgenic recipient hosts did not lead to expansion of these cells or result in islet infiltration, although these TCR7 cells could expand upon transfer into mice expressing high levels of HEL in the serum. Islet cell infiltration only occurred when the TCR7 cells had been polarized to either a Th1 or Th2 phenotype prior to transfer, which led to insulitis. Progression from insulitis to autoimmune diabetes only occurred in these recipients when Th1 but not Th2 TCR7 cells were transferred and CTLA-4 signaling was simultaneously blocked. These findings show that regulatory pathways such as CTLA-4 can hold in check already differentiated autoreactive effector Th1 cells, to inhibit the transition from tolerance to autoimmune diabetes.application/pdfporBreakpoints in immunoregulation required for Th1 cells to induce diabetesNeighbors, MargaretHartley, Suzanne B.Xu, XiulingCastro, António G.Bouley, Donna M.O'Garra, AnneHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONNeighbors, M., Hartley, S. B., Xu, X., Castro, A. G., Bouley, D. M., & O'Garra, A. (2006). Breakpoints in immunoregulation required for Th1 cells to induce diabetes. European journal of immunology, 36(9), 2315-2323PMID16933361ISSNIsPartOf0014-2980,ISSNIsPartOf1521-4141DOIIsPartOf10.1002/eji.2006364322020-10-30T15:32:18Z2006-092006-09-01T00:00:00ZHandlehttps://hdl.handle.net/1822/67936http://purl.org/coar/access_right/c_abf2open accessAdoptive TransferAnimalsAntigens, CDAntigens, DifferentiationCD4-Positive T-LymphocytesCTLA-4 AntigenCell DifferentiationDiabetes Mellitus, Type 1FemaleFlow CytometryInsulinIslets of LangerhansLymphocyte ActivationMiceMice, TransgenicMuramidasePeptidesPromoter Regions, GeneticReceptors, Antigen, T-CellTh1 CellsTh2 CellsTCR-transgenicT helper cellsTolerancehttp://www.oecd.org/science/inno/38235147.pdfFields of Science and Technology (FOS)Ciências Médicas::Medicina Básica397482 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/9973ea6b-b8d7-4ce1-ada9-7caa1ec1a496/download |
| spellingShingle | Breakpoints in immunoregulation required for Th1 cells to induce diabetes Neighbors, Margaret Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| status | SINGLETON |
| subject.fl_str_mv | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance |
| subject.other.fl_str_mv | Ciências Médicas::Medicina Básica |
| title | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| title_full | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| title_fullStr | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| title_full_unstemmed | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| title_short | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| title_sort | Breakpoints in immunoregulation required for Th1 cells to induce diabetes |
| topic | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| topic_facet | Adoptive Transfer Animals Antigens, CD Antigens, Differentiation CD4-Positive T-Lymphocytes CTLA-4 Antigen Cell Differentiation Diabetes Mellitus, Type 1 Female Flow Cytometry Insulin Islets of Langerhans Lymphocyte Activation Mice Mice, Transgenic Muramidase Peptides Promoter Regions, Genetic Receptors, Antigen, T-Cell Th1 Cells Th2 Cells TCR-transgenic T helper cells Tolerance Ciências Médicas::Medicina Básica |
| url | https://hdl.handle.net/1822/67936 |
| visible | 1 |