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

CD 8 + T细胞对于控制大多数病毒感染至关重要，但它们不能消除慢性感染中的病毒。一些研究表明，抑制性受体诱导的CD 8 + T细胞功能衰竭与慢性感染有关。然而，我们和其他人最近表明，效应CD 8 + T细胞在急性病毒感染期间表达高水平的抑制性受体，但在这个时间点具有高度功能。这些结果表明，抑制性受体不一定与T细胞耗竭。我们推测，在慢性病毒急性感染过程中，抑制性受体/配体相互作用可能对病毒感染细胞的免疫逃逸更为重要，从而导致慢性感染。这与我们的初步发现一致，即Friend逆转录病毒感染的细胞在急性感染期间表达高水平的抑制性配体。我们将使用Friend逆转录病毒模型来定义急性逆转录病毒感染晚期抑制性受体/配体的免疫逃逸机制。此外，我们将阻断这种相互作用，以防止病毒慢性化的建立。

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.