Spontaneous recovery from early glomerular inflammation is associated with resistance to anti-GBM glomerulonephritis: tolerance and autoimmune tissue injury.
Different susceptibility to anti-GBM glomerulonephritis (GN) among animal strains has been reported. Using our rat model for T cell-mediated anti-GBM GN, this study initiated an investigation on the mechanism related with GN susceptibility. Anti-GBM GN was induced either through immunization with the nephritogenic T cell epitope pCol(28-40) from Col4alpha3NC1 or through the transfer of specific T cells. WKY rats were highly susceptible to GN while immuno-compatible LEW rats were GN-resistant. GN-resistance in LEW rats was not associated to the immune response to pCol(28-40). First, both strains mounted a Th1 T cell response to pCol(28-40) with identical specificities; transfer of T cells from LEW to WKY rats induced glomerular injury. Second, co-transfer of antibody from WKY to LEW failed to induce GN. Time-course studies revealed that LEW rats did develop T cell-mediated inflammation in glomeruli at early stages similar to WKY rats, as evidenced by histopathology, proteinuria, CD4(+) T cell infiltration in glomeruli, and glomerular expression of inflammatory molecules. However, glomerular inflammation in LEW rats was transient followed by a full recovery. Thus, GN-resistance in LEW rats was due to its ability to contain early T cell-mediated autoimmune glomerular damage. Our model may reveal a potential tolerance mechanism after autoimmune tissue damage has been initiated.
Robertson
Julie
J
Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Wu
Jean
J
Arends
Jon
J
Zhou
Cindy
C
Adrogue
Horacio E
HE
Chan
Jarvis T
JT
Lou
Yahuan
Y
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D024141:Collagen Type IV / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D050533:Glomerular Basement Membrane / Q000276:immunology; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D012075:Remission, Spontaneous; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D018984:Epitopes, T-Lymphocyte