T-cell signal transduction in children with cow's milk allergy -- increased MAP kinase activation in patients with acute symptoms of cow's milk allergy.
The precise immune mechanisms behind cow's milk allergy (CMA) are still unknown. Previously, the production of the cytokines TNF-alpha and IFN-gamma in T cells from children with CMA has been shown to be decreased, and the production of IL-4 has been shown to be increased when compared to healthy children. As these aberrations in cytokine production may be associated with disturbances in cellular function, we investigated whether T-cell signal transduction is abnormal in children with CMA. For this purpose we evaluated the activation of the MAP kinase Erk2. Thirty-nine infants were included in the study. Of those with CMA, 13 had acute symptoms and 9 were free of symptoms due to a successful elimination diet at the time of the study. To activate T cells and to stimulate MAP kinase phosphorylation, peripheral blood mononuclear cells (PBMC) were incubated with Concanavalin A (ConA). The change in MAP kinase phosphorylation was measured by Western blotting. The increase in MAP kinase phosphorylation after stimulation with ConA for 5 min was significantly higher in cells from patients with acute symptoms of CMA than in cells from CMA patients free of symptoms or cells from healthy children. A time-course experiment showed that the change in MAP kinase phosphorylation was still increasing after 10 min incubation in cells from patients with acute symptoms of CMA. The increased MAP kinase activation was found to correlate positively with non-IgE mediated CMA in patients with acute symptoms of CMA.
Osterlund
Pamela
P
Helsinki University Central Hospital, Department of Dermatology, Helsinki, Finland. pamela.osterlund@helsinki.fi
von Willebrand
Maria
M
Andersson
Leif C
LC
Suomalainen
Hanna
H
D015153:Blotting, Western; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D012882:Skin Tests
D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; D019950:Mitogen-Activated Protein Kinase 1