Regulation by intestinal γδ T cells during establishment of food allergic sensitization in mice.
BACKGROUND
Food allergy affects approximately 5% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. The mucosal adjuvant cholera toxin induces allergic sensitization to co-administered proteins in mice, while feeding the protein alone induces oral tolerance. Intestinal γδ T cells could be of importance in the induction of oral tolerance. This study aims to investigate whether γδ T cells have functional relevance in food allergic sensitization.


METHODS
Changes in γδ T cells on days 1, 2, 3, and 7 after initiation of food allergy were evaluated using flowcytometry. Furthermore, the anti-γδ T-cell receptor (TCR) antibody UC7 was used to block the γδ TCR in mice in vivo, followed by sensitization to peanut. After 4 weeks, peanut-specific antibodies in serum and cytokine production in spleen were measured.


RESULTS
Induction of food allergy resulted in a profound decrease in the percentage of γδ T cells in intestinal tissues and Peyer's Patches, but not in mesenteric lymph nodes or spleen. This decrease could be detected from days 1 to 2 after the initiation of food allergy and the number of γδ T cells returned to normal on day 7. Blockade of the γδ TCR resulted in elevated food allergic responses upon sensitization with peanut characterized by increased IgE and Th2 cytokine production in splenocytes.


CONCLUSIONS
These results demonstrate a unique regulatory role of γδ T cells, suggesting that targeting γδ T cells in the intestine may contribute to strategies to prevent and possibly treat food allergy.
Bol-Schoenmakers
M
M
Institute for Risk Assessment Sciences, Utrecht University, Utrecht. m.bol-schoenmakers@uu.nl
Marcondes Rezende
M
M
Bleumink
R
R
Boon
L
L
Man
S
S
Hassing
I
I
Fiechter
D
D
Pieters
R H H
RH
Smit
J J
JJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D010367:Arachis / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007422:Intestines / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D000906:Antibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002772:Cholera Toxin