The Role of the Inhibitory Ligand HVEM and Its Receptors CD160 and BTLA in the Regulation of Anti-retroviral T Cell Responses

Specific CD8+ T cells are crucial for the control of viruses. However, during many chronic viral infections these become dysfunctional. Immune checkpoint receptors, like PD-1 expressed on cells, contribute to this functional suppression infection. acute phase infection virus-specific express high levels but fully competent in killing virus-infected and there is increasing evidence that biological activity inhibitory receptors strongly influenced by availability their respective ligands. We determined expression ligands infected myeloid Friend retroviral (FV) FV granulocytes, monocytes, macrophages increased cell surface PD-L1 recently described ligand HVEM BTLA CD160. In addition, human vitro with HIV also enhanced HVEM. mice, upregulation was accompanied frequencies FV-specific PD-1, CD160 BTLA. To define effects activated FV-infected mice were treated blocking antibodies prevented interaction its two or BTLA, alone combination anti-PD-L1 antibodies. Blocking improved production cytotoxic molecules elimination cells. This effect augmented when therapy combined antibodies, resulting an additional expansion Thus, downregulates functionality potential targets immunomodulatory infections.