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

• Published in: Journal of allergy and clinical immunology 2002-04, Vol.109 (4), p.707-713
• Main Authors: Beyer, Kirsten, Castro, Russell, Birnbaum, Audrey, Benkov, Keith, Pittman, Nanci, Sampson, Hugh A.
• Format: Article
• Language: English
• Subjects: Adolescent; Allergic diseases; Allergies; Biological and medical sciences; Cell growth; Child; Child, Preschool; Cytokines - biosynthesis; Digestive allergic diseases; Eosinophilia - etiology; Female; Food allergies; food allergy; Gastric Mucosa - immunology; Gut; Humans; IL-10; IL-13; IL-4; IL-5; Immunopathology; Infant; Interleukin-10 - physiology; Intestinal Mucosa - immunology; Lymphocyte Activation; Male; Medical sciences; Milk; Milk, Human - immunology; Rodents; T-Lymphocytes - immunology; Th2 Cells - immunology; Transforming Growth Factor beta - physiology; transforming growth factor β
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2002.122503

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, 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-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-13, 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. (J Allergy Clin Immunol 2002;109:707-13.)