In addition to its conventional roles in the innate immune system， complement has been found to directly regulate T cells in the adaptive immune system. Complement components， including C3， C5， and factor D， are important in regulating T cell responses. However， whether complement component C4 is involved in regulating T cell responses remains unclear. In this study， we used a T cell-dependent model of autoimmunity， experimental autoimmune uveitis (EAU) to address this issue. We compared disease severity in wild-type (WT) and C4 knockout (KO) mice using indirect ophthalmoscopy， scanning laser ophthalmoscopy， spectral-domain optical coherence tomography， and histopathological analysis. We a... More
In addition to its conventional roles in the innate immune system， complement has been found to directly regulate T cells in the adaptive immune system. Complement components， including C3， C5， and factor D， are important in regulating T cell responses. However， whether complement component C4 is involved in regulating T cell responses remains unclear. In this study， we used a T cell-dependent model of autoimmunity， experimental autoimmune uveitis (EAU) to address this issue. We compared disease severity in wild-type (WT) and C4 knockout (KO) mice using indirect ophthalmoscopy， scanning laser ophthalmoscopy， spectral-domain optical coherence tomography， and histopathological analysis. We also explored the underlying mechanism by examining T cell responses in antigen-specific recall assays and in T cell priming assays using bone marrow-derived dendritic cells， splenic dendritic cells， and T cells from WT or C4 KO mice. We found that C4 KO mice develop less severe retinal inflammation than WT mice in EAU and show reduced autoreactive T cell responses and decreased retinal T cell infiltration. We also found that T cells， but not dendritic cells， from C4 KO mice have impaired function. These results demonstrate a previously unknown role of C4 in regulating T cell responses， which affects the development of T cell-mediated autoimmunity， as exemplified by EAU. Our data could shed light on the pathogenesis of autoimmune uveitis in humans.
