Autoreactive kidney-infiltrating T-cell clones in murine lupus nephritis.
T-cells have been implicated in autoimmune renal injury. To examine the role of T-cells in lupus nephritis we propagated T-cell clones from the cortical interstitium of MRL/lpr mice. All isolated kidney-infiltrating (KI) T-cell clones [6] express surface markers identical to the T-cells regulated by the lpr gene (Thy 1.2+, TCR alpha/beta +, Lyt-2-, L3T4-, B220+). Although KI T-cell clones have the same surface markers as lymph node-infiltrating (LNI) T-cells, they differ functionally. KI T-cells, but not LNI T-cells, are autoreactive and kidney-specific, exclusively proliferating to renal tubular epithelial (TEC) and mesangial cells. In addition, unlike LNI T-cell supernatants (SN), KI T-cell clones SN induce class II and ICAM-1 on cultured TEC. When KI T-cell clones are injected under the renal capsule, class II is increased on TEC. All clones transcribe mRNA for cytokines capable of inducing class II and ICAM-1 (IL-4, TNF-alpha, IFN-gamma). Anti-IFN-gamma mAb prevents the induction of class II and ICAM-1 on cultured TEC. Since class II and ICAM-1 expression on TEC precedes renal injury, the ability to propagate autoreactive, kidney-specific T-cell clones that induce these molecules provides evidence for their role in initiating renal injury in MRL/lpr mice.
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
C
C
Díaz Gallo
A M
AM
Jevnikar
D C
DC
Brennan
S
S
Florquin
A
A
Pacheco-Silva
V R
VR
Kelley
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002999:Clone Cells; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000502:physiology; D007668:Kidney / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma