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

Abstract

MRL-lpr kidney-infiltrating (KI) T cell clones (CD3+, TCR α/β+ B220+, CD4-, CD8-) are autoreactive, exclusively proliferate to renal tissues, and secrete interferon-γ (IFN-γ). We now report that IFN-γ treatment of tubular epithelial cells (TEC) decreases their ability to induce KI T cell proliferation. The decreased ability of IFN-γ-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-γ. IFN-γ-treated TEC supernatant does not diminish KI T cell proliferation and IFN-γ-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-γ, neither class I, class II, ICAM-1 nor IFN-γ bound to the surface of TEC are responsible. In conclusion, IFN-γ 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-γ represents a self-regulatory mechanism for limiting T cell expansion.