T07003: Investigation of the immunological mechanism inducing cows’ milk sensitive enteropathy

Study Duration: February 1998 to January 2002

Contractor: Royal Free Hospital, London

The aim of this project is to see if there is an association between the behaviour of certain immune cells in children who are allergic to cows’ milk and the general increase in development of allergies of all kinds among children.

There has been marked increase in the incidence of food allergies in the UK and other Western countries in the past few decades, particularly among children, with around 5% of children now showing allergy to cow's milk protein. In addition, sensitisation to milk is now frequently seen in exclusively breast fed infants who become sensitised to milk antigens eaten by their mothers. There has been a suggestion that this increase may not only reflect a broadening of exposure to dietary food antigens in early life, but may also reflect a change in exposure to environmental antigens, such as infectious agents, which may be important for the development of tolerance. The latter is the basis of the so-called 'hygiene hypothesis', which suggests an inverse relationship between hygiene and allergic disease.

While a lot is known about the nature of the sensitising antigen, there has been little study of immune cells within the intestine that may be generated by the presence of a potential food allergen. The aim of this study was to examine the role of the mucosal immune system in cow's milk allergy.

The technique of flow cytometry was used to examine the immune response of proinflammatory lymphocytes (that cause the allergic response) and the regulatory lymphocytes (that regulate the allergic response) from children with or without food allergies before and after challenge with cow's milk protein.

The results indicated that the major difference in children with food allergy was the deficiency of a regulatory lymphocyte population, rather than the excess of proinflammatory cells. This regulatory population, called T_H3 cells, produce a cytokine (TGF-beta) which inhibits the activation of all other cells in the locality. The researchers were able to confirm this finding using the techniques of immunohistochemistry (which identifies the protein) and in situ hybridisation (which identifies the genetic material involved in synthesising the protein).

The researchers concluded that the reduced production of the regulatory cells might result in failure to establish immune tolerance within the intestine, allowing any potentially food-reactive lymphocyte to respond unchecked. They have not established a direct mechanism for generation of these cells, and suggest that further work will be needed for this.

Final report is available from the FSA Library and Information centre. To obtain a copy, please contact the Enquiry Desk, Dr. Elsie Widdowson Library and Information Services, Food Standards Agency (020 7276 8181/8182 or at library&info@foodstandards.gsi.gov.uk).

Contact: Dr Joelle Appleby
Tel: 020 7276 8476
Email: joelle.appleby@foodstandards.gsi.gov.uk