Self-regulation of autoreactive kidney-infiltrating T cells in MRL-lpr nephritis

Kidney Int. 1993 Oct;44(4):692-9. doi: 10.1038/ki.1993.302.

Abstract

MRL-lpr kidney-infiltrating (KI) T cell clones (CD3+, TCR alpha/beta+, B220+, CD4-, CD8-) are autoreactive, exclusively proliferate to renal tissues, and secrete interferon-gamma (IFN-gamma). We now report that IFN-gamma treatment of tubular epithelial cells (TEC) decreases their ability to induce KI T cell proliferation. The decreased ability of IFN-gamma-treated TEC to induce T cell proliferation is evident by 24 hours and can be restored by re-exposure to TEC not treated with IFN-gamma. IFN-gamma-treated TEC supernatant does not diminish KI T cell proliferation and IFN-gamma-treated TEC fixed with glutaraldehyde remain less capable of inducing KI T cell proliferation. Although we have not identified the TEC surface molecule(s) modified by IFN-gamma, neither class I, class II, ICAM-1 nor IFN-gamma bound to the surface of TEC are responsible. In conclusion, IFN-gamma induces a surface alteration(s) on TEC capable of limiting their ability to induce KI T cell proliferation. The ability of autoreactive KI T cells to release IFN-gamma represents a self-regulatory mechanism for limiting T cell expansion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Division / drug effects
  • Cell Movement
  • Cell Survival
  • Clone Cells
  • Homeostasis*
  • Interferon-gamma / pharmacology
  • Kidney / pathology*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Mice
  • Mice, Mutant Strains
  • Nephritis / genetics
  • Nephritis / pathology*
  • Nephritis / physiopathology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Interferon-gamma