CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas
Autoreactive CD8+ and CD4+ T cells have been assigned independent key roles in the destruction of insulin-producing beta cells resulting in type 1 diabetes. Although CD4 help for the generation of efficient CD8+ T cell responses in lymphoid tissue has been extensively described, whether these two ce...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.02001/full |
| _version_ | 1817968600883920896 |
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| author | Gabriel Espinosa-Carrasco Gabriel Espinosa-Carrasco Cécile Le Saout Pierre Fontanaud Thomas Stratmann Patrice Mollard Marie Schaeffer Javier Hernandez |
| author_facet | Gabriel Espinosa-Carrasco Gabriel Espinosa-Carrasco Cécile Le Saout Pierre Fontanaud Thomas Stratmann Patrice Mollard Marie Schaeffer Javier Hernandez |
| author_sort | Gabriel Espinosa-Carrasco |
| collection | DOAJ |
| description | Autoreactive CD8+ and CD4+ T cells have been assigned independent key roles in the destruction of insulin-producing beta cells resulting in type 1 diabetes. Although CD4 help for the generation of efficient CD8+ T cell responses in lymphoid tissue has been extensively described, whether these two cell populations cooperate in islet destruction in situ remains unclear. By using intravital 2-photon microscopy in a mouse model of diabetes, we visualized both effector T cell populations in the pancreas during disease onset. CD4+ T helper cells displayed a much higher arrest in the exocrine tissue than islet-specific CD8+ T cells. This increased arrest was major histocompatibility complex (MHC) class II-dependent and locally correlated with antigen-presenting cell recruitment. CD8+ T cells deprived of continued CD4 help specifically in the pancreas, through blocking MHC class II recognition, failed to maintain optimal effector functions, which contributed to hamper diabetes progression. Thus, we provide novel insight in the cellular mechanisms regulating effector T cell functionality in peripheral tissues with important implications for immunotherapies. |
| first_indexed | 2024-04-13T20:11:14Z |
| format | Article |
| id | doaj.art-e0d8ef67ecea44dfa3859572b658ad7c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T20:11:14Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e0d8ef67ecea44dfa3859572b658ad7c2022-12-22T02:31:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.02001318689CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the PancreasGabriel Espinosa-Carrasco0Gabriel Espinosa-Carrasco1Cécile Le Saout2Pierre Fontanaud3Thomas Stratmann4Patrice Mollard5Marie Schaeffer6Javier Hernandez7INSERM U1183, Institute for Regenerative Medicine and Biotherapy, University of Montpellier, Montpellier, FranceInstitute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceINSERM U1183, Institute for Regenerative Medicine and Biotherapy, University of Montpellier, Montpellier, FranceInstitute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceFaculty of Biology, Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona, SpainInstitute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceInstitute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceINSERM U1183, Institute for Regenerative Medicine and Biotherapy, University of Montpellier, Montpellier, FranceAutoreactive CD8+ and CD4+ T cells have been assigned independent key roles in the destruction of insulin-producing beta cells resulting in type 1 diabetes. Although CD4 help for the generation of efficient CD8+ T cell responses in lymphoid tissue has been extensively described, whether these two cell populations cooperate in islet destruction in situ remains unclear. By using intravital 2-photon microscopy in a mouse model of diabetes, we visualized both effector T cell populations in the pancreas during disease onset. CD4+ T helper cells displayed a much higher arrest in the exocrine tissue than islet-specific CD8+ T cells. This increased arrest was major histocompatibility complex (MHC) class II-dependent and locally correlated with antigen-presenting cell recruitment. CD8+ T cells deprived of continued CD4 help specifically in the pancreas, through blocking MHC class II recognition, failed to maintain optimal effector functions, which contributed to hamper diabetes progression. Thus, we provide novel insight in the cellular mechanisms regulating effector T cell functionality in peripheral tissues with important implications for immunotherapies.http://journal.frontiersin.org/article/10.3389/fimmu.2017.02001/fullautoimmunityCD4 helpeffector CD8+ T cellstype 1 diabetesimagingin vivo |
| spellingShingle | Gabriel Espinosa-Carrasco Gabriel Espinosa-Carrasco Cécile Le Saout Pierre Fontanaud Thomas Stratmann Patrice Mollard Marie Schaeffer Javier Hernandez CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas Frontiers in Immunology autoimmunity CD4 help effector CD8+ T cells type 1 diabetes imaging in vivo |
| title | CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas |
| title_full | CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas |
| title_fullStr | CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas |
| title_full_unstemmed | CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas |
| title_short | CD4+ T Helper Cells Play a Key Role in Maintaining Diabetogenic CD8+ T Cell Function in the Pancreas |
| title_sort | cd4 t helper cells play a key role in maintaining diabetogenic cd8 t cell function in the pancreas |
| topic | autoimmunity CD4 help effector CD8+ T cells type 1 diabetes imaging in vivo |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.02001/full |
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