TY - JOUR
T1 - Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile
AU - Beyer, Kirsten
AU - Castro, Russell
AU - Birnbaum, Audrey
AU - Benkov, Keith
AU - Pittman, Nanci
AU - Sampson, Hugh A.
N1 - Funding Information:
Supported in part by a grant from the National Center of Research Resources-National Institutes of Health (MO1 RR-00071) awarded to the Mt Sinai School of Medicine, in part by a grant from the National Institute of Allergy and Infectious Diseases—NIH (AI44236), and in part by a grant from the Allergy and Immunology Institute of the International Life Science Institute (ILSI) Research Foundation. The opinions expressed herein are those of the authors and do not necessarily represent the views of ILSI.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Food allergy
KW - Gut
KW - IL-10
KW - IL-13
KW - IL-4
KW - IL-5
KW - Transforming growth factor β
UR - http://www.scopus.com/inward/record.url?scp=0036227794&partnerID=8YFLogxK
U2 - 10.1067/mai.2002.122503
DO - 10.1067/mai.2002.122503
M3 - Article
C2 - 11941323
AN - SCOPUS:0036227794
SN - 0091-6749
VL - 109
SP - 707
EP - 713
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -