Renal allograft rejection: protection of renal tubular epithelial cells from lymphokine activated killer cell mediated lysis by pretreatment with cytokines

Abstract

Human renal tissue was disaggregated by passage through a stainless-steel mesh and the resultant material was separated on the basis of particle size. The tubular fraction recovered from a 45 microns mesh was cultured and after a period of between 5 and 7 days outgrowing adherent epithelial cells were identified. All of these cells contained cytokeratin and after culture for at least 14 days fewer than 5% showed surface HLA-DR antigens. Cultured renal epithelial cells were rapidly lysed by lymphokine activated killer (LAK) cells which were produced from peripheral blood lymphocytes of normal subjects by incubation for 5 days in the presence of either recombinant interleukin-2 (IL-2) or mixed lymphocyte reaction (MLR) supernatant. Stimulation of the cultured epithelial cells for 5 days with either gamma-interferon or MLR supernatant resulted in 67% +/- 9% (mean +/- SD; n = 8) of the cells showing an upregulation of HLA-DR expression. These treated cells were markedly less sensitive to lysis by LAK cells than the untreated cells. Thus, if renal cell damaging LAK cells are generated from lymphocytes in vivo by the action of IL-2 produced during rejection, then gamma-interferon, which is also produced during rejection, may partially protect the renal cells from such LAK cell mediated damage.