Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.
OBJECTIVE
Cows' milk proteins have been proposed to play a part in the pathogenesis of Type I (insulin-dependent) diabetes mellitus but both epidemiological and immunological studies have given conflicting results. Thus we aimed to study the immunological response to cows' milk proteins among diabetic and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes.


METHODS
Peripheral blood mononuclear cells from 30 Type I diabetic children (4 to 18 years old) were examined and compared with peripheral blood mononuclear cells from 18 healthy age-matched control children (7 to 15 years old). Expression of IFN-gamma and IL-4 mRNA were detected by realtime RT-PCR and as protein by ELISA after stimulation with BSA, the ABBOS-peptide (a. a. 152-169) and beta-lactoglobulin (betaLG) from cows' milk and ovalbumin from hens' egg. Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive and negative controls, respectively.


RESULTS
Bovine serum albumin caused a weak Th2-like response in Type I diabetic children, whereas BSA antibodies decreased with age only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and betaLG) caused increased expression for IFN-gamma and IL-4 mRNA in diabetic and healthy children. BetaLG caused the strongest immunological response, which decreased with age only among diabetic children. However, ovalbumin from egg caused a similar activation of the immune system and the immune response was similar in both diabetic and healthy children.


CONCLUSIONS
Proteins from cows' milk caused an equal Th1- and Th2-like immune response in diabetic and healthy children. Thus, our results do not support the hypothesis that cows' milk antigens are important for the immune process associated with Type I diabetes.
Karisson
M G
MG
Department of Health and Environment, Clinical Research Center, Faculty of Health Sciences, Linköping University, Sweden. Maria.Karlsson@kfc.liu.se
Garcia
J
J
Ludvigsson
J
J
D000293:Adolescent; D000818:Animals; D000906:Antibodies / Q000097:blood; D000941:Antigens / Q000032:analysis / Q000276:immunology; D002096:C-Peptide / Q000097:blood; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004044:Dietary Proteins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007782:Lactoglobulins / Q000276:immunology; D008297:Male; D008894:Milk Proteins / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D002096:C-Peptide; D004044:Dietary Proteins; D007328:Insulin; D007782:Lactoglobulins; D008894:Milk Proteins; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D012333:RNA, Messenger; C075490:serum albumin, bovine (152-168); D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin