Allergen peptide immunotherapy in humans inhibits allergen-induced proliferation of CD4+ T cells but does not affect suppressive activity of CD4+CD25+ T cells

Abstract

Rationale Our group has previously described immunotherapy using short peptides derived from the major cat allergen Fel d 1, to target CD4+ T cell activation without cross linking IgE. We previously reported that this treatment inhibited allergen late responses, and peripheral blood T cell activation, with increased IL-10 secretion in vitro, and infiltration of CD25+ T cells into allergen challenged skin. In addition we have demonstrated reduced suppressive activity of CD4+CD25+ regulatory T cells in atopic donors. Here, we examined the effect of peptide immunotherapy on regulation by CD4+CD25+ regulatory T cells. Methods 16 patients were entered into a double-blind placebo-controlled trial of an escalating dose regimen of intradermal mix peptides derived from Fel d 1 (total cumulative dose of 291 μg). Peripheral blood CD4+ and CD4+CD25+ T cells were isolated before and after treatment and proliferation to cat allergen extract was measured by thymidine incorporation at 7 days. Results Peptide immunotherapy resulted in significant reduction in the nasal response to allergen challenge (p<0.05) when compared to the placebo-treated group, and this was accompanied by a reduction in cat allergen-induced proliferation of CD4+ T cells (p<0.05). However, there was no change in suppression of cat allergen induced proliferation by CD4+CD25+ T cells. Conclusions Peptide immunotherapy reduces both clinical and CD4+ T cell responsiveness to allergen, but this is not due to increased suppression by CD4+CD25+ T cells.