title: Self-regulation of autoreactive kidney-infiltrating T cells in MRL-lpr nephritis.
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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Gallo
authors.forename: V R
authors.initials: VR
authors.lastname: Kelley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002470:Cell Survival; D002999:Clone Cells; D006706:Homeostasis; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D009393:Nephritis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D007371:Interferon-gamma