Nephrology (Carlton, Vic.) · 2025
CD8+ Regulatory T Cells Induced by Peptide Vaccination Ameliorates Experimental Model of Membranous Nephropathy.
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Chung Edmund Y M, Wang Yuan Min, Shaw Karli, Ronning Emily, Wang Ya, Zhang Geoff Yu, Hu Min, Keung Karen, McCarthy Hugh J, Harris David C H, Stephen Alexander
Аннотация
AIM: CD8+ regulatory T cells (Tregs) are cross-protective across multiple animal models of autoimmunity. Recently, specific peptides from a yeast-peptide-major histocompatibility complex library that expanded CD8+ Tregs in murine experimental multiple sclerosis were reported. Whether these peptides also expand CD8+ Tregs and protect against Heymann nephritis (HN), an experimental model of membranous nephropathy is unknown. We aimed to assess the efficacy of peptide vaccination to induce CD8+ Tregs in HN.
METHODS: Lewis rats were immunised with Fx1A/complete Freund's adjuvant to induce HN and received peptide vaccination 1 week before (prevention vaccination) or 1 week after disease induction (treatment vaccination). To understand whether the effect of peptide vaccination was mediated by CD8+ Tregs, we adoptively transferred CD8+ T cells 1 week after peptide vaccination into HN rats.
RESULTS: Prevention vaccination, but not treatment vaccination, significantly reduced anti-Fx1A autoantibody levels and serum creatinine. Both prevention and treatment vaccination reduced histological kidney injury. mRNA expression of Helios, the major CD8+ Treg transcription factor, was upregulated in both the spleen and kidney with prevention vaccination and in the kidney with treatment vaccination. Adoptive transfer of CD8+ T cells after peptide vaccination significantly reduced serum creatinine, proteinuria, histological kidney injury, anti-Fx1A autoantibody levels, germinal centre formation, and mRNA expression of markers of T follicular helper cells (Bcl6, interleukin-21), T helper 1 cells (interferon-γ, Tbet) and T helper 17 cells (interleukin-6, interleukin-17).
CONCLUSIONS: Peptide vaccination induces CD8+ Tregs that ameliorate induction of experimental membranous nephropathy which may represent a further peripheral regulation of autoimmunity.
METHODS: Lewis rats were immunised with Fx1A/complete Freund's adjuvant to induce HN and received peptide vaccination 1 week before (prevention vaccination) or 1 week after disease induction (treatment vaccination). To understand whether the effect of peptide vaccination was mediated by CD8+ Tregs, we adoptively transferred CD8+ T cells 1 week after peptide vaccination into HN rats.
RESULTS: Prevention vaccination, but not treatment vaccination, significantly reduced anti-Fx1A autoantibody levels and serum creatinine. Both prevention and treatment vaccination reduced histological kidney injury. mRNA expression of Helios, the major CD8+ Treg transcription factor, was upregulated in both the spleen and kidney with prevention vaccination and in the kidney with treatment vaccination. Adoptive transfer of CD8+ T cells after peptide vaccination significantly reduced serum creatinine, proteinuria, histological kidney injury, anti-Fx1A autoantibody levels, germinal centre formation, and mRNA expression of markers of T follicular helper cells (Bcl6, interleukin-21), T helper 1 cells (interferon-γ, Tbet) and T helper 17 cells (interleukin-6, interleukin-17).
CONCLUSIONS: Peptide vaccination induces CD8+ Tregs that ameliorate induction of experimental membranous nephropathy which may represent a further peripheral regulation of autoimmunity.