Cytokine expression in unstimulated PBMC of children with type 1 diabetes and subjects positive for diabetes-associated autoantibodies.
The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to type 1 diabetes. Expression levels of mRNAs specific for each cytokine were determined in peripheral blood mononuclear cells (PBMC) by a multiplex reverse transcription-polymerase chain reaction (RT-PCR) followed by hybridization reactions with lanthanide-labelled probes and detection by time-resolved fluorometry. Newly diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1 signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-beta 1 in comparison with their matched controls (P = 0.0013 and P = 0.012). No significant differences were observed when comparing matched pairs of diabetic children and autoantibody-positive subjects. Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune process, but there was also a reduced level of IFN-gamma expression in the periphery at the onset of clinical diabetes.
Halminen
M
M
JDFI Centre for Diabetes Prevention in Finland, Turku, Finland.
Simell
O
O
Knip
M
M
Ilonen
J
J
D001323:Autoantibodies / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma