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

Background: Food 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. Objective: We sought to determine whether FAHF-2-mediated protection could be extended long-term and explored the mechanisms underlying its persistent immunomodulatory effects. Methods: Peanut-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. Results: Food 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 IgG_2a levels were increased as much as 60%, and these effects persisted over time. T_H2 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. Conclusions: Food 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.