Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates
| العنوان: | Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates |
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| المؤلفون: | Simon Ville, Gilles Blancho, Paul Baker, Lyssia Belarif, Stéphanie Le Bas-Bernardet, Nicolas Poirier, David Minault, Jeremy Hervouet, Elisabeth Cassagnau, Bernard Vanhove, Caroline Mary, Nahzli Dilek, Linda Scobie, Melanie Chevalier |
| المساهمون: | Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Effimune SAS [Nantes], Department of Life Sciences [Glasgow, UK], Glasgow Caledonian University (GCU), Centre hospitalier universitaire de Nantes (CHU Nantes), The Progreffe Foundation and the Centaure Foundation (France), the Institut Hospitalo-Universitaire–Centre Européen des Sciences de la Transplantation et d’Immunothérapie project, supported by Nantes Metropole and the Pays de la Loire Region., European Project, Le Bihan, Sylvie, European Union FP7 Health Program Grant ECGA 281493 - INCOMING |
| المصدر: | Journal of Immunology Journal of Immunology, 2016, 196 (1), pp.274-283. ⟨10.4049/jimmunol.1501810⟩ Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2016, 196 (1), pp.274-283. ⟨10.4049/jimmunol.1501810⟩ |
| بيانات النشر: | HAL CCSD, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Immunology, Priming (immunology), Autoimmunity, chemical and pharmacologic phenomena, Biology, medicine.disease_cause, Lymphocyte Activation, B7-H1 Antigen, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Immune system, CD28 Antigens, T-Lymphocyte Subsets, medicine, Immunology and Allergy, Animals, Humans, CTLA-4 Antigen, IL-2 receptor, Skin, Inflammation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Recall, CD28, hemic and immune systems, Papio anubis, 030104 developmental biology, medicine.anatomical_structure, Virus Activation, Memory T cell, Immunologic Memory, CD80, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Signal Transduction |
| الوصف: | Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1–dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell–mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1501810⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee6e639f003499feaa606422bec78a78 https://www.hal.inserm.fr/inserm-02150299/document |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee6e639f003499feaa606422bec78a78 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00221767 15506606 |
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| DOI: | 10.4049/jimmunol.1501810⟩ |