In recent years evidence has been accumulated suggesting an important role of the complement system in the induction and promotion of T cell immunity to viral infections. In a Friend retrovirus (FV) mouse model C3 has been shown to serve as a natural adjuvant for the expansion of virus-specific CTLs at early time points of infection. Furthermore, the local production of complement anaphylatoxins C3a and C5a, generated during complement activation has been shown to up-regulate co-stimulatory molecules on both naive CD4+ T cells and DCs providing survival signals for effector T cells. Additionally, these anaphylatoxins and their corresponding receptors C3aR and C5aR have recently been shown to directly regulate the development and function of both natural and induced Tregs. In the absence of signaling via C3aR and C5aR conventional CD4+ T cells become FoxP3+ iTregs through auto-inductive TGF-ß1 expression. Similarly, signaling through C3aR and C5aR abrogate the function of nTreg by controlling Foxp3 expression. Thus C3 and C5 produced locally during APC-T cell interactions by both DCs and also by T cells seem to have a crucial role in the polarization of CD4+ T cell towards effector vs. regulatory subsets.
Thus, in our proposal we will investigate the role of complement in the generation of Tregs during FV infection.
about
faculty members
students
dates
publications
application
news
innsbruck
contact
