Cell-mediated immunity in interstitial nephritis. I. T Lymphocyte systems in nephritic guinea pigs: The natural history and diversity of the immune response

Guinea pigs immunized with renal tubular antigens develop a severe interstitial nephritis. The complete expression of disease depends on a complex interplay between cellular and humoral mechanisms. The present studies were undertaken to analyze the lymphocyte diversity engendered during the course of this nephropathy. The results demonstrated a strong cellular recognition of the sensitizing antigens, as well as the concomitant development of a potent nonspecific suppressor system. Sequential analyses indicated that reactive T cells from different anatomic compartments maintained these distinctive functions. Judged from isotope incorporation studies, lymphocytes harvested from peritoneal exudates were more likely to recognize sensitizing renal tubular antigens than either spleen, lymph node, or peripheral blood cells. Lymph node cells, however, were more efficient in mediating the intense polyclonal immunosuppression that was typically present in nephritic animals after 1 week of disease. Delayed hypersensitivity measurements confirmed the in vivo presence of this immunosuppression. All of these observed T cell functions were fully developed before the appearance of anti-tubular antibodies in the kidneys of diseased animals. Eventually, however, the cellular recognition of the sensitizing antigens started to decline in the face of continued suppression and pathologic damage along cortical tubules. These findings are discussed in terms of the complex role of T lymphocytes in the pathogenesis and regulatory modulation of interstitial kidney disease.