Szépfalusi Z, Nentwich I, Jost E, Gerstmayr M, Ebner C, Frischer T, Urbanek R
Department of Pediatrics, University of Vienna, Austria.
J Allergy Clin Immunol. 1998 Apr;101(4 Pt 1):514-20. doi: 10.1016/s0091-6749(98)70359-8.
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.
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.
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.
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.
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.
水解奶粉（HFs）适用于对牛奶蛋白过敏的婴儿，出于预防目的，也适用于无法进行母乳喂养的易患特应性疾病的新生儿。HFs的最终特性不仅是降低变应原性，还包括降低免疫原性，同时兼具良好的口感和热量值。关于HFs诱导免疫反应的能力尚无相关信息。
我们试图确定部分水解奶粉（pHF）和深度水解奶粉（eHF）的残余免疫原性，并研究10种不同HFs诱导的脐血来源（n = 71）单核细胞的细胞反应性。
为测试HF对辅助性T细胞的影响，建立了来自牛奶过敏个体的β-酪蛋白特异性T细胞克隆（TCCs，n = 21），并在HF刺激下测定T细胞增殖和细胞因子谱（干扰素-γ和白细胞介素-4）。
我们发现与牛奶蛋白相比，eHF的增殖反应显著降低。基于乳清的pHF显示出与未改性牛奶蛋白相同的增殖能力。正如预期的那样，与部分水解产品相比，深度加工的乳清产品显示出较低的细胞反应（pHF乳清与eHF乳清相比，p < 0.0001）。基于酪蛋白的pHF和基于酪蛋白的eHF之间未发现细胞反应差异。β-酪蛋白特异性TCCs（n = 21）对酪蛋白衍生的水解产物有增殖反应（基于酪蛋白/乳清的pHF为14%，基于酪蛋白的pHF为4%，基于酪蛋白的eHF为0%）。还发现基于乳清的pHF能诱导β-酪蛋白特异性TCCs增殖，表明存在或产生了与这些乳清衍生水解产物具有交叉反应性的肽。用基于乳清或酪蛋白的pHF或eHF刺激的TCCs产生的细胞因子（白细胞介素-4、干扰素-γ）与用未改性产品刺激的相同克隆产生的细胞因子量相同。
我们的数据表明，基于乳清和酪蛋白的eHFs在T细胞水平上显示出高度降低的免疫原性。相比之下，pHFs在T细胞水平上显示出可检测到的残余免疫原性，反映出诱导具有致病重要性的T细胞反应的可能性。
