title: Cord blood mononuclear cells and milk-specific T-cell clones are tools to evaluate the residual immunogenicity of hydrolyzed milk formulas.
abstract: BACKGROUND
  Hydrolyzed milk formulas (HFs) are given to infants allergic to cow's milk proteins and, for preventive reasons, to atopy-prone newborns for which breast feeding is not feasible. The ultimate properties of HFs are not only a reduced allergenicity but also decreased immunogenic capacity combined with good taste and caloric value. No information is available concerning the capacity of HFs to induce immune responses.
  
  
  OBJECTIVE
  We sought to determine the residual immunogenic capacity of partially (pHF) and extensively hydrolyzed milk formula (eHF), and we studied the cellular reactivity of cord blood-derived (n = 71) mononuclear cells induced by 10 different HFs.
  
  
  METHODS
  To test the effect of HF on T-helper cells, beta-casein-specific T-cell clones (TCCs, n = 21) from individuals allergic to milk were established, and T-cell proliferation and cytokine profiles (interferon-gamma and IL-4) were determined on stimulation with HF.
  
  
  RESULTS
  We found significantly reduced proliferative responses of eHF compared with milk proteins. Whey-based pHF displayed the same proliferative capacity as unmodified milk proteins. As expected, extensively processed whey products displayed lower cellular responses compared with partially hydrolyzed products (pHF whey vs eHF whey, p < 0.0001). No difference in cellular response was found between casein-based pHF and casein-based eHF. Beta-casein-specific TCCs (n = 21) proliferated in response to casein-derived hydrolysates (14% with casein/whey-based pHF, 4% with casein-based pHF, and 0% with casein-based eHF). Whey-based pHF was also found to induce proliferation in beta-casein-specific TCCs, indicating the presence or the generation of peptides displaying cross-reactivity with these whey-derived hydrolysates. TCCs stimulated with whey- or casein-based pHF or eHF produced the same amount of cytokines (IL-4, interferon-gamma) as the same clones stimulated with unmodified products.
  
  
  CONCLUSIONS
  Our data indicate that whey- and casein-derived eHFs display highly reduced immunogenic properties at the T-cell level. In contrast, pHFs display residual immunogenic properties detectable at the T-cell level, reflecting a potential for the induction of pathogenetically important T-cell responses.
authors.affiliation: Department of Pediatrics, University of Vienna, Austria.
authors.forename: Z
authors.initials: Z
authors.lastname: Szépfalusi
authors.forename: I
authors.initials: I
authors.lastname: Nentwich
authors.forename: E
authors.initials: E
authors.lastname: Jost
authors.forename: M
authors.initials: M
authors.lastname: Gerstmayr
authors.forename: C
authors.initials: C
authors.lastname: Ebner
authors.forename: T
authors.initials: T
authors.lastname: Frischer
authors.forename: R
authors.initials: R
authors.lastname: Urbanek
mesh_terms: D000328:Adult; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008892:Milk / Q000276:immunology*; D008894:Milk Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D008894:Milk Proteins