Complement and regulatory T cells: The effect of complement on regulatory T cell responses in a mouse retrovirus model.
Final Report Abstract
Establishment of chronic viral infections might be a consequence of the induction and the expansion of regulatory T cells (Tregs). Growing evidence suggests that dendritic cells (DC) are involved in the expansion of Tregs, but the mechanisms of DC-Treg interaction are still elusive. Viruses that are opsonized with complement components have been shown to efficiently infect DC and thus might influence Treg responses. Using the Friend virus (FV) model, a mouse model for chronic retroviral infections, we found a delayed Treg expansion in knock-out mice deficient for the complement component C3. Surprisingly, this resulted only in a minor effect on anti-viral CD8 T cell responses or viral loads. However, we could demonstrate that virus particle opsonization (C3) was important for an efficient infection of DCs by the virus and both complement receptors CD11b and CD11c contributed to this effect. In the contrary to our original hypothesis, we were unable to experimentally demonstrate that FV-infected DCs preferentially expand Tregs. Overall, complement components do not seem to play a dominating role in the induction of Treg responses after virus infection, but clearly modulate anti-viral T cell responses by mechanisms that remain not fully understood.
Publications
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2019. Fcγ Receptor Type I (CD64)-Mediated Impairment of the Capacity of Dendritic Cells to Activate Specific CD8 T Cells by IgG-opsonized Friend Virus. Viruses. 11:E145
Bánki Z, Werner R, Riepler L, Rössler A, Müllauer B, Hegen V, Bayer W, Verbeek JS, Dittmer U, Stoiber H
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2019. Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity. FEMS Microbiol Rev. 43:435-456
Dittmer U, Sutter K, Kassiotis G, Zelinskyy G, Bánki Z, Stoiber H, Santiago ML, Hasenkrug KJ
