Regulatory T cells in chronic viral infections

Regulatory Tcells (Treg) have gained much attention within the last years and are described to be of crucial necessity in inhibiting autoimmunity and transplant rejection in mice and human. Recent observations provide evidence for a role of Treg in the case of chronic infection, where certain viruses exploit Treg cells to circumvent efficient killing of infected cells by cytotoxic Tcells (CTL). This leads to lifelong persistency of the virus in the host. Worldwide about 250 million people are affected by chronic infections only of HIV and the hepatitis C virus (HCV). The induction of Treg cells by HIV is already documented and evidence has also been provided for HCV infection. To study the modes of Treg cell induction and their impact on the immunesystem, a mouse model has been developed. Friend virus, a murine retrovirus which chronically infects mice is a perfect candidate for the experiments. This study aims to first clarify the antigen specificity of Treg cells induced by Friends virus infection. Treg cells suppress their counterparts by cell-cell contact, the molecules involved in this interaction with CTL are not yet identified and will be characterized as a second approach in this study. Third the question will be addressed, whether memory Tcells are controled by Treg cells. This will yield data that will help to understand the interplay of Treg cells, which are induced by infection of mice, and CTL. Abrogating the suppressive effects pharmaceutically could be a valuable therapeutic approach to eradicate persistent viruses from the host and consequently to improve the clinical outcome.