The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/11/1775/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1775-1784

Articles

Permanent CD8+ T Cell Depletion Prevents Proteinuria in Active Heymann Nephritis

Mark J. Penny, Rochelle A. Boyd, and Bruce M. Hall

From the Department of Medicine, Liverpool Hospital and the University of New South Wales, Liverpool, New South Wales 2170, Australia

Active Heymann nephritis (HN) is a rat model of human idiopathic membranous nephropathy in which injury is thought to be mediated by membrane attack complex of complement (MAC) activated by antibody (Ab) to glomerular epithelial cells. Recent work has shown that HN develops in C6-deficient rats which cannot assemble MAC, and that infiltration of activated cytotoxic CD8+ T cells and macrophages into glomeruli coincides with proteinuria. This study examined the role of CD8+ T cells in mediating glomerular injury in HN by permanent CD8+ cytotoxic T cell depletion via adult thymectomy (ATx) and anti-CD8 mAb. Groups of rats were depleted of CD8+ T cells either before immunization for HN or 6 wk after immunization when Ab responses and glomerular IgG deposition were well established. These were compared with groups of HN, ATx/HN, and complete Freund's adjuvant (CFA) controls. Neither group of CD8+ T cell–depleted rats developed proteinuria, although there was normal development and deposition of Ab. CD8+ T cell–depleted rats developed neither T cell or macrophage infiltrates nor their effector cytokines, 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 concluded that CD8+ cytotoxic T cells are essential to the mediation of glomerular injury in HN and may be relevant to the pathogenesis and treatment of membranous nephropathy.

Key Words: Heymann nephritis • glomerulonephritis • rat • CD8+ T lymphocyte • lymphocyte depletion

Address correspondence to Mark Penny, Department of Medicine, Liverpool Hospital, Liverpool, New South Wales 2170, Australia. Phone: 61-2-9828-3000; Fax: 61-2-9828-4970; E-mail: pennymark{at}bigpond.com

Portions of this work were previously published as abstracts: Penny, M.J., R.A. Boyd, and B.M. Hall. 1996. CD8+ T cell depletion prevents proteinuria in active Heymann nephritis. Kidney Int. 51:1325. (Abstr.)

Australian and New Zealand Society of Nephrology 32nd Annual Scientific Meeting, Perth, Australia.

Penny, M.J., R.A. Boyd, and B.M. Hall. 1996. CD8+ T cell depletion impairs proteinuria in active Heymann nephritis. J.A.S.N. 7:1715. (Abstr.)

29th American Congress of Nephrology, New Orleans, USA.

Penny, M.J., R.A. Boyd, and B.M. Hall. 1997. CD8+ T cell depletion prevents proteinuria in active Heymann nephritis.

XIVth Congress of the International Society of Nephrology, Sydney, Australia.

Abbreviations used: ANOVA, analysis of variance; ATx, adult thymectomy; GEC, glomerular epithelial cells; GN, glomerulonephritis; HN, Heymann nephritis; iNOS, inducible nitric oxide synthase; IP, immunoperoxidase; MAC, membrane attack complex (of complement); RT-PCR, reverse transcription PCR.


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