Combined T regulatory cell and Th2 expression profile identifies children with cow's milk allergy.
The role of T regulatory cells in spontaneous recovery from cow's milk allergy (CMA) is unclear. We investigated the mRNA expression of 12 T-cell markers and the protein expression of CD4, CD25, CD127, FoxP3 after in vitro beta-lactoglobulin stimulation of peripheral blood mononuclear cells from children with persisting CMA (n=16), early recovery (n=20) or no atopy (n=21). Artificial neural networks with exhaustive search for all marker combinations revealed that markers FoxP3, Nfat-C2, IL-16 and GATA-3 distinguished patients with persisting CMA most accurately from other study groups. FoxP3 mRNA expression following beta-lactoglobulin stimulation was highest in children with persisting CMA. Also the FoxP3 intensity in CD4(+) CD25(high)CD127(low) cells was higher in children with CMA compared with non-atopic children. The expression profile of both Th2- and T regulatory cell-related genes thus reflects the clinical activity of CMA. Tolerance, in contrast, is not characterized by activation of circulating T regulatory cells.
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
Emma M
EM
Savilahti
Sirkku
S
Karinen
Harri M
HM
Salo
Paula
P
Klemetti
Kristiina M
KM
Saarinen
Timo
T
Klemola
Mikael
M
Kuitunen
Sampsa
S
Hautaniemi
Erkki
E
Savilahti
Outi
O
Vaarala
D000818:Animals; D002417:Cattle; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D019410:Interleukin-16 / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007782:Lactoglobulins / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D016571:Neural Networks, Computer; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D019410:Interleukin-16; D053699:Interleukin-7 Receptor alpha Subunit; D007782:Lactoglobulins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human