Induction of CD137 expression by viral genes reduces T cell costimulation

• Published in: Journal of cellular physiology 2019-11, Vol.234 (11), p.21076-21088
• Main Authors: Wu, Meihui, Wong, Hiu Yi, Lin, Jia Le, Moliner, Annalena, Schwarz, Herbert
• Format: Article
• Language: English
• Subjects: Antigen-presenting cells; Antigens; CD137; CD137 antigen; Cytotoxicity; EBV; Epstein-Barr virus; Feedback; Gene expression; HTLV‐1; immune evasion; Immune response; Immune response (cell-mediated); Immune system; Immunity; Immunosurveillance; Intracellular; Ligands; LMP‐1; Lymphocytes; Lymphocytes T; Membrane proteins; Negative feedback; Pathogens; Plasma membranes; Tax; Viruses
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28710

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. Epstein‐Barr virus and human T‐cell lymphotropic virus‐1 induce the expression of CD137 on infected T cells. CD137 is transferred by trogocytosis to CD137L‐expressing antigen presenting cells, 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 viruses from immune surveillance.