Regulatory T Cells Control the Th1 Immune Response in Murine Crescentic Glomerulonephritis

Kidney Int. 2011 Jul;80(2):154-64. doi: 10.1038/ki.2011.108. Epub 2011 Apr 27.

Abstract

Crescentic glomerulonephritis is mediated by inappropriate humoral and cellular immune responses toward self-antigens that may result from defects in central and peripheral tolerance. Evidence now suggests that regulatory T cells (Tregs) may be of pathophysiological importance in proliferative and crescentic forms of glomerulonephritis. To analyze the role of endogenous Tregs in a T cell-dependent glomerulonephritis model of nephrotoxic nephritis, we used 'depletion of regulatory T cell' (DEREG) mice that express the diphtheria toxin receptor under control of the FoxP3 (forkhead box P3) gene promoter. Toxin injection into these mice efficiently depleted renal and splenic FoxP3(+) Treg cells as determined by fluorescent-activated cell sorting (FACS) and immunohistochemical analyses. Treg depletion exacerbated systemic and renal interferon-γ (IFNγ) expression and increased recruitment of IFNγ-producing Th1 cells into the kidney without an effect on the Th17 immune response. The enhanced Th1 response, following Treg cell depletion, was associated with an aggravated course of glomerulonephritis as measured by glomerular crescent formation. Thus, our results establish the functional importance of endogenous Tregs in the control of a significantly enhanced systemic and renal Th1 immune response in experimental glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemotaxis
  • Disease Models, Animal
  • Glomerulonephritis / immunology*
  • Immunity, Cellular / immunology*
  • Interferon-gamma / biosynthesis
  • Kidney / immunology
  • Kidney / pathology
  • Lymphocyte Depletion
  • Mice
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*

Substances

  • Interferon-gamma