Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile

Abstract

Background: A number of gastrointestinal disorders, including allergic eosinophilic gastroenteritis and food protein-induced enteropathy, have been associated with milk hypersensitivity. The immunologic reactions appear to involve T cells that are activated by specific food proteins.

Objective: The present study was performed to examine the cytokine profiles of milk-specific lymphocytes from the duodenal lamina propria from children with milk-induced gastrointestinal diseases.

Methods: Duodenal biopsy specimens obtained from 10 patients with allergic eosinophilic gastroenteritis, food protein-induced enteropathy, or both and 12 control subjects were mechanically minced and cultured with either mitogens (i.e., polyclonal T-cell expansion) or milk proteins (i.e., milkspecific T-cell expansion). By using flow cytometry, expanded T cells were phenotyped with anti-CD4, anti-CD8, anti-IL-4, anti-IL-5, and anti-IFN-gamma mAbs. The milk specificity of the lines was evaluated by means of the lymphocyte proliferation assay. In addition, the release of T(H)1, T(H)2, and T(H)3 cytokines was determined after restimulation.

Results: In patients and control subjects polyclonal expansion of mucosal lymphocytes resulted in predominantly T(H)1 cells. Milk-specific mucosal T-cell lines could be established in 60% of the patients but in none of the control subjects. In contrast to the polyclonal expansion of T cells, the milk-specific expansion of mucosal T cells showed a clear T(H)2 cytokine profile. On restimulation with milk protein, these cells showed a high proliferative response. They released T(H)2 cytokines, predominately IL-13, but failed to release T(H)3 cytokines important in the development of oral tolerance.

Conclusion: The release of T(H)2 cytokines after stimulation of milk-specific mucosal T cells may play a pathogenic role in the inflammatory changes seen in milk-induced gastrointestinal disorders.