Cell-mediated immunity in interstitial nephritis. II. T lymphocyte effector mechanisms in nephritic guinea pigs: analysis of the renotropic migration and cytotoxic response.

The present studies investigate the effector role of lymphocytes in guinea pigs with an interstitial nephritis. Several observations were made relative to a number of functions expressed by these cells. The results of adoptive cell migration studies suggest that a subpopulation of T cells in nephritic animals traffic renotropically to either normal or damaged kidneys on transfer. Similar lymphocytes were also tested in vitro for direct effector function by utilizing target kidney cell monolayers in a cell-mediated cytotoxicity assay. The kinetics of the observed cytotoxic response were studied over the life span of nephritic animals. Optimal target-cell lysis occurred 12 to 17 days after sensitization, simultaneous with the onset of active histopathologic changes. The cytotoxicity was stoichiometrically titratable and relatively specific for fetal kidney tissue. In addition, cells from the spleen or lymph nodes of diseased animals effectively suppressed this cytotoxic response. These findings demonstrate that a diverse population of T lymphocytes are both capable of damaging the renal interstitium as well as modulating effector-cell functions on a regional basis with the immune system.