Transgenic tubular cell expression of class II is insufficient to initiate immune renal injury.
Autoimmune disease in mouse models of lupus nephritis is associated with enhanced renal tubular epithelial cell (TEC) expression of major histocompatibility complex (MHC) class II (Ia) molecules. It is unknown whether de novo TEC expression of syngeneic la alone can initiate immune attack or whether expression is secondary to cytokines released by infiltrating lymphocytes. To establish if the expression of high levels of self-MHC molecules alone can initiate immune renal injury in the adult animal, kidneys from transgenic C57BL/6 (B6) mice (Ins-I-E) bearing constitutively high levels of I-Eb on proximal TEC were transplanted into nephrectomized male B6 x C3H F1 hybrid mice (I-Eb/k). Control mice received kidneys from I-Eb negative, nontransgenic B6 mice, and all transplant recipient mice were evaluated for renal disease. At the end of the study (> 8.3 months mean survival), the transgenic transplant recipients did not become proteinuric (< 1+ urinary protein) and had normal serum creatinine levels (control = 95 +/- 8 versus transgenic transplants = 116 +/- 23 mumol/L; N = four/group), and the kidneys remained histologically normal. These results establish that the expression of high levels of transgenic MHC class II molecules on TEC is insufficient to initiate autoimmune injury in this model. It is suggested that, in addition to MHC class II molecules, other signals or accessory molecules are required from TEC to initiate immune renal injury.
Jevnikar
A M
AM
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Singer
G G
GG
Coffman
T
T
Glimcher
L H
LH
Kelley
V E
VE
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006824:Hybridization, Genetic; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009393:Nephritis / Q000276:immunology*
D000949:Histocompatibility Antigens Class II