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 (ie, polyclonal T-cell expansion) or milk proteins (ie, milk-specific 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-γ mAbs. The milk specificity of the lines was evaluated by means of the lymphocyte proliferation assay. In addition, the release of TH1, TH2, and TH3 cytokines was determined after restimulation. Results: In patients and control subjects polyclonal expansion of mucosal lymphocytes resulted in predominantly TH1 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 TH2 cytokine profile. On restimulation with milk protein, these cells showed a high proliferative response. They released TH2 cytokines, predominately IL-IS, but failed to release TH3 cytokines important in the development of oral tolerance. Conclusion: The release of TH2 cytokines after stimulation of milk-specific mucosal T cells may play a pathogenic role in the inflammatory changes seen in milk-induced gastrointestinal disorders.