Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes
| Autor: | Isabelle Dunand-Sauthier, Walter Reith, Marie-Laure Santiago-Raber, Carla Lippens, Vishal Agrawal, Beatris Mastelic-Gavillet, Kerstin Sarter, Claire-Anne Siegrist, Fernanda V. Duraes, Florian Gobet, Giovanni Magistrelli, Ulla Ravn, Elisa Leimgruber, Stéphanie Hugues, Nicolas Fischer, Arun T. Kamath, Paola Fontannaz, Emmanuèle Barras, Leslie Guéry |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Encephalomyelitis Autoimmune Experimental Regulatory T cell T cell Genes MHC Class II Immunology Antigen-Presenting Cells Regulatory Factor X Transcription Factors ddc:616.07 CD8-Positive T-Lymphocytes Biology Cancer Vaccines Cell Line Mice 03 medical and health sciences medicine Animals Humans Immunology and Allergy Cytotoxic T cell RNA Messenger IL-2 receptor Antigen-presenting cell Research Articles Mice Knockout Immunity Cellular Membrane Glycoproteins Butyrophilins Brief Definitive Report Nuclear Proteins biochemical phenomena metabolism and nutrition Acquired immune system Natural killer T cell Molecular biology 3. Good health DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Trans-Activators CD8 Transcription Factors |
| Zdroj: | J Exp Med The Journal of Experimental Medicine The Journal of experimental medicine Journal of Experimental Medicine, Vol. 213, No 2 (2016) pp. 177-187 |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Butyrophilins are proteins secreted during lactation and thought to influence immune function. Sarter et al. generated butyrophilin-2a2–deficient mice to show enhanced effector T cell responses, antitumor responses, and exacerbated EAE due to the impaired APC modulation of T cell immunity. Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2−/− mice exhibited enhanced effector CD4+ and CD8+ T cell responses, impaired CD4+ regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen-presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell–mediated immunity. |
| Databáze: | OpenAIRE |
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