| First Author | Haas C | Year | 1997 |
| Journal | J Immunol | Volume | 158 |
| Issue | 11 | Pages | 5484-91 |
| PubMed ID | 9164971 | Mgi Jnum | J:40633 |
| Mgi Id | MGI:707988 | Doi | 10.4049/jimmunol.158.11.5484 |
| Citation | Haas C, et al. (1997) IFN-gamma is essential for the development of autoimmune glomerulonephritis in MRL/Ipr mice. J Immunol 158(11):5484-91 |
| abstractText | MRL/lpr mice develop lymphoproliferation and accelerated autoimmune glomerulonephritis from which they ultimately die. To investigate the role of IFN-gamma in the manifestation of the disease, we generated MRL/lpr mice lacking the IFN-gamma receptor (MRL/lpr gamma R -/-), The absence of IFN-gamma signaling had no effect on generalized lymphoproliferation, expansion of CD4(-)CD8(-) double-negative T cells, or hypergammaglobulinemia. By contrast, glomerulonephritis as detected by proteinuria and histology was absent in MRL/lpr gamma R -/- mice, While serum IgG1 anti-dsDNA Abs were increased in all three strains of MRL/lpr mice (gamma R +/+, +/-, -/-), those of the IgG2a and IgG3 isotypes were low in MRL/lpr gamma R -/- mice, Immune complexes and C3 deposition were dramatically reduced in the glomerular capillaries of MRL/lpr gamma R -/- mice compared with MRL/lpr gamma R+/+ and +/- mice, Therefore, IFN-gamma plays a key regulatory role in the development of nephritis in MRL/lpr mice, Low levels of IFN-gamma-dependent IgG2a and IgG3 autoantibodies in MRL/lpr gamma R -/- mice might protect them from the pathogenic features of IgG3 cryoglobulins and complement-activating IgG2a and IgG3. |
