Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gamma-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-gamma-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(H)2 cytokine production by CD4(+) T cells from FAHF-2-treated mice was reduced as much as 75%, whereas CD8(+) T-cell IFN-gamma production was markedly increased by as much as 85% at the final challenge. Neutralization of INF-gamma 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-gamma production.
Srivastava
Kamal D
KD
Department of Pediatrics, Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY, USA.
Qu
Chunfeng
C
Zhang
Tengfei
T
Goldfarb
Joseph
J
Sampson
Hugh A
HA
Li
Xiu-Min
XM
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D010367:Arachis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; C497376:Food Allergy Herbal Formula-2; D010936:Plant Extracts; D007073:Immunoglobulin E; D006632:Histamine; D007371:Interferon-gamma