Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells

BackgroundFood allergy is a serious and sometimes fatal condition for which there is no cure. We previously reported that Food Allergy Herbal Formula (FAHF)–2) protected peanut-allergic mice against anaphylactic reactions as long as 4 weeks posttherapy. This formula is now in clinical trials in the United States.ObjectiveWe sought to determine whether FAHF-2–mediated protection could be extended long-term and explored the mechanisms underlying its persistent immunomodulatory effects.MethodsPeanut-allergic mice received FAHF-2 daily orally by gavage for 7 weeks, and then received 7 oral peanut challenges at intervals of 4 to 10 weeks over a period of 36 weeks. For mechanistic studies, some mice received CD4+ or CD8+ T-cell–depleting antibodies or IFN-γ–neutralizing antibodies. Anaphylactic symptoms, body temperatures, and plasma histamine levels were recorded after each challenge, and peanut-specific immunoglobulin levels and cytokine profiles of splenocytes, mesenteric lymph node cells, and purified CD4+ and CD8+ T cells were determined.ResultsFood Allergy Herbal Formula-2 treatment protected mice from anaphylaxis for more than 36 weeks after discontinuing treatment. Peanut-specific IgE levels were reduced as much as 50%, whereas IgG2a levels were increased as much as 60%, and these effects persisted over time. TH2 cytokine production by CD4+ T cells from FAHF-2–treated mice was reduced as much as 75%, whereas CD8+ T-cell IFN-γ production was markedly increased by as much as 85% at the final challenge. Neutralization of INF-γ and depletion of CD8+ T cells markedly attenuated FAHF-2 efficacy.ConclusionsFood Allergy Herbal Formula-2 provides long-term protection from anaphylaxis by inducing a beneficial shift in allergen-specific immune responses mediated largely by elevated CD8+ T-cell IFN-γ production.