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

• Published in: Journal of allergy and clinical immunology 2009-02, Vol.123 (2), p.443-451
• Main Authors: Srivastava, Kamal D., MPhil, Qu, Chunfeng, MD, PhD, Zhang, Tengfei, PhD, Goldfarb, Joseph, PhD, Sampson, Hugh A., MD, Li, Xiu-Min, MD
• Format: Article
• Language: English
• Subjects: Allergens - administration & dosage; Allergens - immunology; Allergens - pharmacology; Allergy and Immunology; anaphylaxis; Anaphylaxis - immunology; Anaphylaxis - prevention & control; Animals; Arachis - immunology; Arachis hypogaea; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cytokines - biosynthesis; Cytokines - drug effects; Cytokines - immunology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histamine - blood; IgE; Immunoglobulin E - blood; Interferon-gamma - immunology; Interferon-gamma - metabolism; Lymphocyte Depletion; Medical sciences; Mice; Mice, Inbred C3H; murine model; Peanut allergy; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - prevention & control; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T cells; T H2 cytokines; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism; traditional Chinese herbal medicine
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2008.12.1107

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 IgG2a levels were increased as much as 60%, and these effects persisted over time. TH 2 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.