Cytokine secretion patterns in twins discordant for Type I diabetes.
OBJECTIVE
The search for T-cell reactions that are associated with disease in Type I (insulin-dependent) diabetes mellitus is severely hampered because control groups cannot be matched for relevant immune response genes. We therefore compared T-cell responses between identical twins discordant for Type I diabetes.


METHODS
Pairs of monozygotic twins (n = 17) discordant for Type I diabetes were studied. Cultures were set up from whole blood immediately after sampling and cells were challenged with human recombinant hsp60, with the mitogen phytohaemagglutinin or with the staphylococcal superantigen. Supernatants were removed after 48 or 96 h and analysed for T-helper1 type cytokines interferon-gamma, TNFalpha and T-helper2 type cytokines IL-4, IL-10 by sandwich-ELISA.


RESULTS
The height of the T-helper1 type cytokine response to hsp60, phytohaemagglutinin or staphylococcal enterotoxin B did not show disease association, i. e. it was similar between discordant twins. In contrast, the production of T-helper2 type cytokines differed between discordant twins. The IL-10 response to hsp60 was higher in twins at low disease risk (islet cell antibody-negative) than in their diabetic cotwins (p < 0.01), as was the IL-4 response to phytohaemagglutinin (p < 0.05). No difference was seen in the cytokine response between islet cell antibody-positive twins and their diabetic cotwins.


CONCLUSIONS
The data indicate an association between T-helper2 type cytokine secretion patterns and disease or disease risk.
Kallmann
B A
BA
Diabetes Research Institute, Heinrich-Heine-University of Düsseldorf, Germany.
Lampeter
E F
EF
Hanifi-Moghaddam
P
P
Hawa
M
M
Leslie
R D
RD
Kolb
H
H
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004200:Diseases in Twins; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014430:Twins, Monozygotic
D018834:Chaperonin 60; D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma