title: TNF receptor 1 mediates dendritic cell maturation and CD8 T cell response through two distinct mechanisms.
abstract: TNF-α and its two receptors (TNFR1 and 2) are known to stimulate dendritic cell (DC) maturation and T cell response. However, the specific receptor and mechanisms involved in vivo are still controversial. In this study, we show that in response to an attenuated mouse hepatitis virus infection, DCs fail to mobilize and up-regulate CD40, CD80, CD86, and MHC class I in TNFR1(-/-) mice as compared with the wild-type and TNFR2(-/-) mice. Correspondingly, virus-specific CD8 T cell response was dramatically diminished in TNFR1(-/-) mice. Adoptive transfer of TNFR1-expressing DCs into TNFR1(-/-) mice rescues CD8 T cell response. Interestingly, adoptive transfer of TNFR1-expressing naive T cells also restores DC mobilization and maturation and endogenous CD8 T cell response. These results show that TNFR1, not TNFR2, mediates TNF-α stimulation of DC maturation and T cell response to mouse hepatitis virus in vivo. They also suggest two mechanisms by which TNFR1 mediates TNF-α-driven DC maturation, as follows: a direct effect through TNFR1 expressed on immature DCs and an indirect effect through TNFR1 expressed on naive T cells.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xilai
authors.initials: X
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shi
authors.forename: Peishuang
authors.initials: P
authors.lastname: Du
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Hongyu
authors.initials: H
authors.lastname: Deng
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D004306:Dose-Response Relationship, Immunologic; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D016056:Immunodominant Epitopes; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha