title: Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: key role for IL-10.
abstract: BACKGROUND
  The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood.
  
  
  OBJECTIVE
  The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated.
  
  
  METHODS
  Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status.
  
  
  RESULTS
  Cow's milk-specific TCCs of children with persistent CMA were T(H)2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-gamma and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25.
  
  
  CONCLUSIONS
  The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk-tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-gamma. These findings suggest that activated CD4(+) T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.
authors.affiliation: Department of Dermatology/Allergology, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands.
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Tiemessen
authors.forename: Adrie G
authors.initials: AG
authors.lastname: Van Ieperen-Van Dijk
authors.forename: Carla A f m
authors.initials: CA
authors.lastname: Bruijnzeel-Koomen
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Edward F
authors.initials: EF
authors.lastname: Knol
authors.forename: Els
authors.initials: E
authors.lastname: Van Hoffen
mesh_terms: D000293:Adolescent; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002417:Cattle; D002648:Child; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016269:Milk Hypersensitivity / Q000276:immunology*; D008894:Milk Proteins / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018793:Interleukin-13; D008894:Milk Proteins; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma