title: A functional complement system is required for normal T helper cell differentiation.
abstract: 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.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland. pirkka.pekkarinen@helsinki.fi
authors.forename: Pirkka T
authors.initials: PT
authors.lastname: Pekkarinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaali
authors.forename: Sami
authors.initials: S
authors.lastname: Junnikkala
authors.forename: Laura H
authors.initials: LH
authors.lastname: Rossi
authors.forename: Heli
authors.initials: H
authors.lastname: Tuovinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
chemical_list: D003176:Complement C3; D007132:Immunoglobulin Isotypes; D003165:Complement System Proteins