CD8+ REGULATORY T CELLS INDUCED BY PEPTIDE VACCINATION AMELIORATES EXPERIMENTAL MEMBRANOUS NEPHROPATHY
Edmund Chung1, Yuan M Wang1, Karli Shaw1, Emily Ronning1, Geoff Y Zhang1, Min Hu2, Karen Keung3, Hugh McCarthy1, David C Harris2, Stephen I Alexander1 1The Centre For Kidney Research, The Children’s Hospital At Westmead, Westmead, NSW, Australia2Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, Westmead, NSW, Australia3Department of Nephrology, Prince of Wales Hospital, Randwick, NSW, Australia
Abstract
Aim: To assess the efficacy of peptide vaccination to expand CD8+ regulatory T cells (Tregs) in Heymann nephritis (HN), an experimental model of membranous nephropathy.
Background: CD8+ Tregs are cross-protective across multiple animal models of autoimmunity including multiple sclerosis (MS), type 1 diabetes and membranous nephropathy using T cell vaccination. Recently, specific peptides from a yeast peptide major histocompatibility complex library that clonally expand CD8+ Tregs in experimental MS were reported. Whether these peptides also expand CD8+ Tregs and protect against HN is unknown.
Methods: Lewis rats were immunised with Fx1A/complete Freund’s adjuvant (CFA) to induce HN and received either peptide vaccination 7 days before (preventative vaccination) or 7 days after disease induction (treatment vaccination). To understand whether the effect of peptide vaccination was mediated by CD8+ Tregs, we adoptively transferred CD8+ T cells 7 days after peptide vaccination into HN rats. Control rats were immunised with CFA alone.
Results: Preventative vaccination, but not treatment vaccination, significantly reduced anti-Fx1A autoantibody levels and serum creatinine. Both preventative and treatment vaccination reduced glomerulosclerosis, tubular injury, and interstitial infiltrate compared to untreated HN rats. While there were no between-group differences in total CD8+ T cells on flow cytometry, mRNA expression of Helios, the major CD8+ Treg transcription factor, was upregulated in both the spleen and kidney of preventative and treatment vaccination rats compared to untreated HN rats. Adoptive transfer of CD8+ T cells after peptide vaccination also significantly reduced anti-Fx1A autoantibody levels, serum creatinine, proteinuria and histological kidney injury compared to untreated HN rats.
Conclusion: Peptide vaccination induces CD8+ Tregs that ameliorate induction of experimental membranous nephropathy which may represent a further peripheral control against autoimmunity.
Biography
Edmund Chung is an adult nephrologist and is currently undertaking a PhD studying immune mechanisms underpinning membranous nephropathy. He completed a Master of Clinical Epidemiology and is the Knowledge Translation and Dissemination Editor for the Cochrane Kidney and Transplant Group. He is interested in better understanding the pathogenesis of glomerulonephritis and translating improved treatment options into clinical care.