Complement-dependent enhancement of CD8+ T cell immunity to lymphocytic choriomeningitis virus infection in decay-accelerating factor-deficient mice.
Decay-accelerating factor (DAF, CD55) is a GPI-anchored membrane protein that regulates complement activation on autologous cells. In addition to protecting host tissues from complement attack, DAF has been shown to inhibit CD4+ T cell immunity in the setting of model Ag immunization. However, whether DAF regulates natural T cell immune response during pathogenic infection is not known. We describe in this study a striking regulatory effect of DAF on the CD8+ T cell response to lymphocytic choriomeningitis virus (LCMV) infection. Compared with wild-type mice, DAF knockout (Daf-1(-/-)) mice had markedly increased expansion in the spleen of total and viral Ag-specific CD8+ T cells after acute or chronic LCMV infection. Splenocytes from LCMV-infected Daf-1(-/-) mice also displayed significantly higher killing activity than cells from wild-type mice toward viral Ag-loaded target cells, and Daf-1(-/-) mice cleared LCMV more efficiently. Importantly, deletion of the complement protein C3 or the receptor for the anaphylatoxin C5a (C5aR) from Daf-1(-/-) mice reversed the enhanced CD8+ T cell immunity phenotype. These results demonstrate that DAF is an important regulator of CD8+ T cell immunity in viral infection and that it fulfills this role by acting as a complement inhibitor to prevent virus-triggered complement activation and C5aR signaling. This mode of action of DAF contrasts with that of CD59 in viral infection and suggests that GPI-anchored membrane complement inhibitors can regulate T cell immunity to viral infection via either a complement-dependent or -independent mechanism.
Fang
Chongyun
C
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Miwa
Takashi
T
Shen
Hao
H
Song
Wen-Chao
WC
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis; D003176:Complement C3 / Q000235:genetics / Q000502:physiology*; D015936:Complement C5a / Q000235:genetics / Q000502:physiology*; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D018958:CD55 Antigens; D016827:CD8 Antigens; D003176:Complement C3; D015936:Complement C5a