title: Kidney-infiltrating CD4+ T-cell clones promote nephritis in lupus-prone mice.
abstract: In systemic lupus erythematosus, CD4+ T cells play key roles in the initiation and promotion of autoantigen-specific humoral immunity, and indirect evidence suggests that T cells are pathogenic effectors in lupus nephritis. The contribution of kidney-infiltrating T cells to nephritis, however, has not been verified because of the difficulty in directly analyzing organ-infiltrating T cells. Here, we examined the pathogenic roles of autoreactive cytokine-expressing CD4+ T cells from the kidneys of early nephritic MRL/lpr mice. Interferon (IFN)-γ-secreting cells were enriched among CD5(high)CD4+ T cells found in the inflamed kidneys. Using single-cell analysis of the T-cell receptor (TCR)(high)CD5(high)CD4+ T cells from the kidneys of early nephritic MRL/lpr mice, two IFN-γ-expressing CD4+ T cell clones, MLK2 and MLK3, were identified. CD4+ T cells transduced with the T-cell receptor genes from each clone responded to splenic dendritic cells in an MHC class II-dependent manner, but not to B cells or macrophages. MLK3-transduced CD4+ T cells proliferated in the spleens of prenephritic mice, promoted nephritis progression upon adoptive transfer, and enhanced the deposition of C3 without promoting anti-double-stranded DNA antibody production. Thus, CD4+ T cells in the inflamed kidneys of MRL/lpr mice contribute to nephritis progression.
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors: Akiko
authors: A
authors: Okamoto
authors: Keishi
authors: K
authors: Fujio
authors: Nelson H
authors: NH
authors: Tsuno
authors: Koki
authors: K
authors: Takahashi
authors: Kazuhiko
authors: K
authors: Yamamoto
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018956:CD5 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018450:Disease Progression; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma