NDLI: Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mary, Caroline Poirier, Nicolas Chevalier, Melanie Hervouet, Jeremy Baker, Paul Le Bas-Bernardet, Stephanie Vanhove, Bernard Ville, Simon Scobie, Linda Minault, David Dilek, Nahzli Cassagnau, Elisabeth Blancho, Gilles Belarif, Lyssia
Description	Author Affiliation: Poirier N ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Chevalier M ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Mary C ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Hervouet J ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Minault D ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Baker P ( Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, United Kingdom.); Ville S ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Le Bas-Bernardet S ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Dilek N ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Belarif L ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Cassagnau E ( Centre Hospitalier Universitaire, 44000 Nantes, France); Scobie L ( Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, United Kingdom.); Blancho G ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France); Vanhove B ( INSERM UMR 1064, Institut de Transplantation Urologie Néphrologie, Université de Nantes, 44000 Nantes, France)
Abstract	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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	196
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2016-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd28 Antagonists & Inhibitors Autoimmune Diseases Drug Therapy Immunologic Memory Immunology Inflammation Skin T-lymphocyte Subsets Animals Antigens, Cd274 Autoimmunity Ctla-4 Antigen Lymphocyte Activation Papio Anubis Signal Transduction Pathology Virus Activation Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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