Kidney-infiltrating CD4+ T-cell clones promote nephritis in lupus-prone mice

Kidney Int. 2012 Nov;82(9):969-79. doi: 10.1038/ki.2012.242. Epub 2012 Jul 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • CD5 Antigens / metabolism
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Disease Progression
  • Gene Expression / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology*
  • Macrophages / cytology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred MRL lpr
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Spleen / cytology
  • Spleen / immunology


  • CD5 Antigens
  • Cd5 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interferon-gamma