Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab.
Food allergy is a major public health problem, for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cow's milk allergy undergoing a novel and rapid high-dose oral desensitization protocol enabled by treatment with omalizumab (anti-immunoglobulin (Ig)E monoclonal antibodies). Within a week of treatment, the CD4(+) T-cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4(+) T cells. Over the following 3 months while the subjects remained on high doses of daily oral milk, the CD4(+) T-cell response returned, characterized by a shift from interleukin-4 to interferon-γ production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high-dose oral allergen desensitization may be associated with deletion of allergen-specific T cells, without the apparent development of allergen-specific Foxp3(+) regulatory T cells.
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
D
D
Bedoret
A K
AK
Singh
V
V
Shaw
E G
EG
Hoyte
R
R
Hamilton
R H
RH
DeKruyff
L C
LC
Schneider
K C
KC
Nadeau
D T
DT
Umetsu
D000284:Administration, Oral; D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002417:Cattle; D002478:Cells, Cultured; D002648:Child; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008892:Milk / Q000009:adverse effects; D016269:Milk Hypersensitivity / Q000276:immunology / Q000628:therapy*; D008894:Milk Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D000069444:Omalizumab; D058408:Th1-Th2 Balance
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D008894:Milk Proteins; D015847:Interleukin-4; D000069444:Omalizumab; D007073:Immunoglobulin E; D007371:Interferon-gamma