Cell-mediated immunity in interstitial nephritis. III. T lymphocyte-mediated fibroblast proliferation and collagen synthesis: an immune mechanism for renal fibrogenesis.

Fibroblast proliferation and collagen synthesis play an important role in the progression of intersititial nephritis. To evaluate the involvement of immune mechanisms in this process, we induced intersititial nephritis in guinea pigs utilizing injections of tubular antigens. Over a 3-week period, injected animals developed a nephritis characterized by mononuclear infiltrates and expanding areas of fibrotic scar formation. Involved kidneys contained increased collagen as compared to controls. To identify mediators of the observed fibrogenesis, T lymphocytes from nephritic and control animals were stimulated with soluble tubular antigens. Dialyzed supernatants from control lymphocyte cultures contained an inhibitor of both fibroblast proliferation and collagen synthesis. In contrast, supernatants from nephritic animals demonstrated absence of inhibition and a progressively increasing titer of a factor that enhanced both kidney fibroblast proliferation and collagen synthesis. As the disease progressed, however, nephritic lymphocytes also began secreting an inhibitor of proliferation that could be detected in low levels. These studies suggest, therefore, that immune mechanisms and altered lymphocyte function may play an important role in the development, progression, and regulation of renal fibrogenesis in intersititial nephritis.