DNA VACCINATION AGAINST SPECIFIC PATHOGENIC T CELL RECEPTORS REDUCES PROTEINURIA IN ACTIVE HEYMANN NEPHRITIS

Wu H, Walters G, Alexander SI and Knight JF
Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, 2145

We have previously identified potential pathogenic T cells within glomeruli that use T cell receptors (TCR) encoding V 5, V 7 and V 13 in combination with J in Heymann nephritis (HN)¹, a rat autoimmune disease model of human membranous nephritis This study is to test whether DNA vaccination specifically targeting these three TCR V chains alters the disease course. Lewis rats were vaccinated with naked DNA encoding the identified TCRs. Two weeks after DNA immunisation, the rats were challenged with Fx1A in complete Freund's adjuvant (CFA) to induce HN. DNA vaccination targeting V 5, V 7 and V 13 with J 2.6 significantly protected against disease compared with control groups (HN group and DNA vaccination with V 8 group). Proteinuria was reduced at 6, 8, 10 and 12 weeks after immunisation of Fx1A (P‹0.001). IgG2a auto-antibodies to Fx1A (P‹0.05), glomerular infiltrates of macrophages and CD8+ T cells (P‹0.005) and glomerular IFN- R expression (P‹0.01) were also decreased. This specific T cell intervention significantly reduces the severity of active Heymann nephritis. DNA vaccination targeting the T cell receptors of pathogenic T cells is an attractive therapeutic alternative to broad immunosuppression in the treatment of glomerulonephritis.

1. Walters,G., Wu,H. & Knight,J.F. Glomerular T cells in Heymann nephritis. - Clin Exp Immunol 2001 Nov;126(2):319-25. 319-325 (2001).

Presented at Australian and New Zealand Society of Nephrology (ANZSN). 38th Annual Scientific Meeting. Sydney, NSW, 2-4 Sept 2002