The role of inhibitory receptors and their ligands in immune escape from CD8+ T cells and the establishment of chronic virus infection

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CD8+ T cells are critical for the control of most virus infections but they cannot eliminate virus in chronic infections. Several studies imply that functional exhaustion of CD8+ T cells induced by inhibitory receptors is associated with chronic infection. However, we and others have recently shown that effector CD8+ T cells express high levels of inhibitory receptors during acute viral infections but are highly functional at this time point. These results indicate that inhibitory receptors are not necessarily associated with T cell exhaustion. We hypothesize that during acute infections with chronic viruses inhibitory receptor/ligand interaction might be more important for immune escape of virus-infected cells, which can then result in chronic infection. This is in line with our preliminary finding that Friend retrovirus-infected cells express high levels of inhibitory ligands during acute infection. We will use the Friend retrovirus model to define the mechanisms of immune escape by inhibitory receptors/ligands during the late phase of acute retroviral infection. In addition, we will block this interaction to prevent the establishment of viral chronicity.