CORD-BLOOD MONONUCLEAR-CELLS AND MILK-SPECIFIC T-CELL CLONES ARE TOOLS TO EVALUATE THE RESIDUAL IMMUNOGENICITY OF HYDROLYZED MILK FORMULAS

Background: Hydrolyzed milk formulas (HFs) are given to infants allerg ic to cow's milk proteins and, For preventive reasons, to atopy-prone newborns for which breast feeding is not feasible, The ultimate proper ties of HFs are not only a reduced allergenicity but also decreased im munogenic capacity combined with good taste and caloric value. No info rmation is available concerning the capacity of HFs to induce immune r esponses. Objective: We sought to determine the residual immunogenic c apacity of partially (pHF) and extensively hydrolyzed milk formula (eH F), and we studied the cellular reactivity of cord blood-derived (n = 71) mononuclear cells induced by 10 different HFs. Methods: To test th e 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 significant ly reduced proliferative responses of eHF compared with milk proteins. Whey-based pHF displayed the same proliferative capacity as unmodifie d milk proteins. As expected, extensively processed whey products disp layed lower cellular responses compared with partially hydrolyzed prod ucts (pHF whey vs eHF whey, p < 0.0001). No difference in cellular res ponse was found between casein-based eHF and casein-based eHF. beta-Ca sein-specific TCCs (n = 21) proliferated in response to casein-derived hydrolysates (14% with casein/whey-based pHF), 4% with casein-based p HF, and 0% with casein-based eHF). Whey-based pHF was also found to in duce proliferation in beta-casein-specific TCCs, indicating the presen ce or the generation of peptides displaying cross-reactivity with thes e whey-derived hydrolysates. TCCs stimulated with whey- or casein-bhas ed pHF or eHF produced the same amount of cytokines (IL-4, interferon- gamma) as the same clones stimulated with unmodified products. Conclus ion: Our data indicate that whey- and casein-derived eHFs display high ly reduced immunogenic properties at the T-celI level. In contrast, pH Fs display residual immunogenic properties detectable at the T cell le vel, reflecting a potential for the induction of pathogenetically impo rtant T-cell responses.