Early nutritional events have the potential to affect health outcomes in later life including the development of allergy. Food allergy is usually the first manifestation of allergy. Breastfeeding has been associated with a protective effect against the development of allergy, but the evidence is contradictory and the mechanisms involved are not clear. We hypothesize that milk cytokines, such as transforming growth factor  (TGF-), play a role in regulating immune responses to dietary antigens. Using a rat pup model of gastrostomy feeding, the immune response profile, at weaning and post-weaning, of allergy-prone Brown Norway rats fed formula supplementation with TGF- was assessed. We show that feeding formula to allergy-prone rat pups results in increased total IgE immunoglobulin, -lactoglobulin (BLG) IgG1 antibody, and mucosal mast cell activation, as measured by serum rat mast cell protease II (RMCPII) levels in the gut. Supplementation of formula with physiological levels of TGF- down-regulated the BLG IgG1 response as well as total IgE and mucosal mast cell activation. Supplementation of formula also resulted in an increase in Th1 cytokines, interleukin (IL)-18, IL-12p40, IL-12p35, and interferon gamma (IFN-␥) and an increase in IL-10. In conclusion, TGF- supplementation of formula moved the immune response profile of allergy prone (Th2 type) rat pups toward a Th1 profile in the suckling period. Importantly, this immune profile persisted after weaning when TGF- was no longer present in the diet. (Pediatr Res 59: 650-655, 2006) E arly nutritional events have the potential to effect health outcomes in later life (1,2) including allergy development. Allergic disease arises due to complex interactions between genetic predisposition and environment including early nutritional events (3). Hereditary factors are important in the development of allergy as infants who go onto develop allergic disease show an early predisposition to Th2 responses to allergens in the first year of life. These responses are short-lived in infants without a predisposition to allergy (4). The mechanism involved in allergy development is at present unclear, although the ability to mount a Th1 immune response is important in preventing persistent Th2 immune responses and development of allergic disease. An imbalance favoring Th2 type immune responses increases the risk of allergic disease.Food allergy is usually the first manifestation of allergy with susceptible children going on to develop inhalant allergies as well (5). While the incidence of inhalant allergy is increasing, the incidence of food allergy is relatively stable (6). Breast-feeding has been associated with a protective effect against the development of allergy, but the evidence is contradictory and there is debate as to whether breast milk prevents or reduces the incidence of allergic disease (7,8). Van Odijk et al. (6) have carried out a multidisciplinary review of the literature on early feeding and impact on later allergy and concluded that breast-feeding...