Induction of CD137 expression by viral genes reduces T cell costimulation
| Autor: | Herbert Schwarz, Annalena Moliner, Hiu Yi Wong, Meihui Wu, Jia Le Lin |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Herpesvirus 4 Human Genes Viral Trogocytosis Physiology T-Lymphocytes T cell Clinical Biochemistry Antigen-Presenting Cells Biology Lymphocyte Activation Deltaretrovirus Virus Mice Tumor Necrosis Factor Receptor Superfamily Member 9 03 medical and health sciences 0302 clinical medicine Immune system Cricetinae medicine Animals Humans Cytotoxic T cell Antigen-presenting cell Virulence Intracellular parasite CD137 Cell Biology Cell biology Tumor Virus Infections 4-1BB Ligand 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Tumor Escape |
| Zdroj: | Journal of Cellular Physiology. 234:21076-21088 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.28710 |
| Popis: | Intracellular pathogens are subject to elimination by a cellular immune response, and were therefore under evolutionary pressure to develop mechanisms that allow them to inhibit especially this arm of immunity. CD137, a T cell costimulatory molecule, and its ligand, CD137 ligand (CD137L), which is expressed on antigen presenting cells (APC), are potent drivers of cellular cytotoxic immune responses. Here, we report that different viruses usurp a negative feedback mechanism for the CD137-CD137L system that weakens cellular immune responses. Latent membrane protein (LMP)-1 and Tax, oncogenes of Epstein-Barr virus (EBV), and human T-cell lymphotropic virus (HTLV)-1, respectively, induce the expression of CD137. CD137 is transferred by trogocytosis to CD137L-expressing APC, and the CD137-CD137L complex is internalized and degraded, resulting in a reduced CD137-mediated T cell costimulation and a weakened cellular immune response which may facilitate the escape of the virus from immune surveillance. These data identify the usurpation of a CD137-based negative feedback mechanism by intracellular pathogens that enables them to reduce T cell costimulation. |
| Databáze: | OpenAIRE |
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