PERMANENT CD8(-CELL DEPLETION PREVENTS PROTEINURIA IN ACTIVE HEYMANN NEPHRITIS() T)

Active Heymann nephritis (HN) is a rat model of human idiopathic membr anous nephropathy in which injury is thought to be mediated by membran e attack complex of complement (MAC) activated by antibody (Ab) to glo merular epithelial cells. Recent work has shown that HN develops in CG -deficient rats which cannot assemble MAC, and that infiltration of ac tivated cytotoxic CD8(+) T cells and macrophages into glomeruli coinci des with proteinuria. This study examined the role of CD8(+) T cells i n mediating glomerular injury in HN by permanent CD8(+) cytotoxic T ce ll depletion via adult thymectomy (ATx) and anti-CD8 mAb. Groups of ra ts were depleted of CD8(+) T cells either before immunization for HN o r 6 wk after immunization when Ab responses and glomerular IgG deposit ion were well established. These were compared with groups of HN, ATx/ HN, and complete Freund's adjuvant (CFA) controls. Neither group of CD 8(+) T cell-depleted rats developed proteinuria, although there was no rmal development and deposition of Ab. CD8(+) T cell-depleted rats dev eloped neither T cell or macrophage infiltrates nor their effector cyt okines, which are present in glomeruli of rats with HN. Examination of lymph node (LN) draining sites of immunization showed these findings were not explained by altered immune events within these LNs. It was c oncluded that CD8+ cytotoxic T cells are essential to the mediation of glomerular injury in HN and may be relevant to the pathogenesis and t reatment of membranous nephropathy.