Analysis of T cells and major histocompatibility complex class I and class II mRNA and protein content and distribution in antiglomerular basement membrane disease in the rabbit.
The major interacting components of the immune system, major histocompatibility complex (MHC) class I and class II proteins and T cells were analyzed in a model of anti-GBM (glomerular basement membrane) disease in the rabbit that progresses to develop cellular crescents and glomerular and interstitial fibrosis. Class I and II mRNA and protein were measured in isolated glomeruli and whole renal cortex using cDNA probes and monoclonal antibodies. The distribution of T cells and class I and II proteins was assessed by immunofluorescence. Normal glomeruli contained no T cells and were class II negative. By day 4, glomeruli contained MHC class I and II mRNA and protein and class II positive T cells. Although some animals had T cells in the periglomerular area, these cells were class II negative. By day 7 periglomerular T cells were largely class II positive (activated) and there was increased MHC class I and II mRNA and protein in whole renal cortex. Later T cells accumulated in the tubulo-interstitial compartment, which became diffusely positive for MHC classes I and II, but to a variable extent in different animals. Those with high class II mRNA expression also had detectable T cell antigen receptor mRNA by Northern analysis. The authors conclude 1) in this model there was a close association between mRNA abundance and protein expression for both MHC classes I and II in glomeruli and renal cortex as a whole; 2) in this model of glomerular injury there are three phases of activation. The first phase takes place in the glomerulus and is associated with accumulation of activated T cells and MHC class I and II protein in the glomerulus. Phase 2 is associated with the accumulation of periglomerular T cells and their becoming class II positive. There is subsequent dissemination (phase 3) of activated T cells and accumulation of class I and II mRNA and protein throughout the interstitial compartment. This spacial progression of glomerulocentric inflammation is likely associated with degree of injury and permanent loss of renal function.
Eldredge
C
C
Department of Internal Medicine, University of Michigan, Ann Arbor.
Merritt
S
S
Goyal
M
M
Kulaga
H
H
Kindt
T J
TJ
Wiggins
R
R
D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics*; D007672:Kidney Cortex / Q000737:chemistry / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000473:pathology*
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D004247:DNA