Complement C5a receptor is essential for the optimal generation of antiviral CD8⁺ T cell responses

The complement system has been long regarded as an important effector of the innate immune response. Furthermore, complement contributes to various aspects of B and T cell immunity. Nevertheless, the role of complement in CD8⁺ T cell antiviral responses has yet to be fully delineated. We examined the CD8⁺ T cell response in influenza type A virus-infected mice treated with a peptide antagonist to C5aR to test the potential role of complement components in CD8⁺ T cell responses. We show that both the frequency and absolute numbers of flu-specific CD8⁺ T cells are greatly reduced in C5aR antagonist-treated mice compared with untreated mice. This reduction in flu-specific CD8⁺ T cells is accompanied by attenuated antiviral cytolytic activity in the lungs. These results demonstrate that the binding of the C5a component of complement to the C5a receptor plays an important role in CD8⁺ T cell responses.