A functional complement system is required for normal T helper cell differentiation.

Complement is a fundamental part of the innate immune system, and also modulates B cell responses. Its effects on T cells, however, are less well studied. Here we have studied antigen-specific T cell responses in C3-knockout (C3-KO) C57BL/6 mice. The animals were immunized with ovalbumin (OVA) in complete Freund's adjuvant, which favors T helper 1 (Th1)-type responses. Splenic lymphocytes from C3-KO mice proliferated less in response to OVA stimulation than splenocytes from control wild type (WT) mice. The response in the C3-KO mice was also qualitatively different. The expression of Th1 lineage determining transcription factor T-bet was decreased in OVA-stimulated splenocytes, and the induction of Th1-associated IgG subclasses impaired. In WT mice T cell proliferation in response to OVA was positively correlated with antigen-specific IgG2a and IgG3 levels. In C3-KO mice the proliferative response correlated with antigen-specific IgE levels, consistent with Th2 deviation. The expression of Th1-inducing cytokines IL-12 and IFN-γ was also decreased in the collecting lymph nodes in the C3-KO mice after immunization. Our results show that the complement system and its component C3 participate in the regulation of T cell responses, and that complement function is required for normal T helper cell differentiation.