Bystander suppression of experimental arthritis by nasal administration of a heat shock protein peptide

Abstract

p1 immune therapy induces a population of CD4 T cells with reduced TNFα and increased peptide-specific IFNγ production at the site of inflammation. This population expresses FoxP3 and has potent suppressive capacity which, upon transfer, protects against arthritis. The bystander epitope p1 may therefore be a suitable candidate for antigen-specific immunotherapy in arthritis.

Pep19 drives epitope spreading in periodontitis and periodontitis‐associated autoimmune diseases

“…The reason for the dissimilar observations remains to be clarified. We are currently devising an immunotherapeutic strategy to induce peptide-specific tolerance or bystander suppression through selfpeptide administration by oral or nasal routes that has been shown to suppress rheumatoid arthritis (39)(40)(41).…”

“…Results: A dominant immune response exclusively to Pep19 prevailed in healthy human subjects (before the age of 40) and mice that persisted in chronic periodontitis and autoimmune diseases without being replaced further by subsequent subdominant epitopes. A sequential epitope spreading provoked by Pep19 to subdominant autoantigen peptide 19 from human HSP60 (Hu19) in most healthy human subjects and mice, and to autoantigen peptide 9 from human HSP60 (Hu9) and neoantigen oxidized low-density lipoprotein (ox-LDL) in P. gingivalis-induced chronic periodontitis and autoimmune diseases could be demonstrated in a reproducible and predictable manner.…”

Peptide immunotherapy in experimental autoimmune encephalomyelitis

“…Heat shock proteins (HSPs) are candidate antigens to serve as molecular "flags" for attracting suppressive T cells to inflamed tissues. [56] Nasal application of peptides from HSP60 or HSP70 was able to promote Foxp3+ T cells with suppressive function in arthritis models in rat [57] and mouse, [58] respectively. Similarly, nasal application of a peptide from rat HSP60 was able to modulate MBP-driven EAE in rats.…”

TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis

“…Peptide immune therapy has been shown to shift immune responses towards a regulatory phenotype using in-vivo animal models of autoimmune disease and in-vitro culture systems of patient cells 1–8. Extension of these results into human trials has so far been promising but limited in scope 9–14.…”

“…One of the major issues that hampered peptide mucosal tolerance clinical trials from happening is that the amount of experimental support that mucosal vaccination can elicit detectable peptide-specific immune responses is still limited. Although peptide-specific cytokine production was detected in some studies indicating deviation of the immune response, a clear increase in peptide-specific T cells is most often lacking 2 5 8. As a consequence, clear assessment of the proposed immune deviation and monitoring the efficacy of the immune intervention in patients had been challenging.…”