title: Decay-accelerating factor regulates T-cell immunity in the context of inflammation by influencing costimulatory molecule expression on antigen-presenting cells.
abstract: Recent studies have indicated a role of complement in regulating T-cell immunity but the mechanism of action of complement in this process remains to be clarified. Here we studied mice deficient in decay-accelerating factor (DAF), a key membrane complement regulator whose deficiency led to increased complement-dependent T-cell immune responses in vivo. By crossing OT-II and OT-I T-cell receptor transgenic mice with DAF-knockout mice, we found that lack of DAF on T cells did not affect their responses to antigen stimulation. Similarly, lack of DAF on antigen-presenting cells (APCs) of naive mice did not alter their T-cell stimulating activity. In contrast, APCs from DAF-knockout mice treated with inflammatory stimuli were found to be more potent T-cell stimulators than cells from similarly treated wild-type mice. Acquisition of higher T-cell stimulating activity by APCs in challenged DAF-knockout mice required C3 and C5aR and was correlated with decreased surface PD-L1 and/or increased CD40 expression. These findings implied that DAF suppressed T-cell immunity as a complement regulator in the context of inflammation but did not play an intrinsic role on T cells or APCs. Collectively, our data suggest a systemic and indirect role of complement in T-cell immunity.
authors.affiliation: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Chongyun
authors.initials: C
authors.lastname: Fang
authors.forename: Takashi
authors.initials: T
authors.lastname: Miwa
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Song
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D018958:CD55 Antigens / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D003167:Complement Activation / Q000276:immunology*; D005434:Flow Cytometry; D007249:Inflammation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D018958:CD55 Antigens