Aberrant regulation of interleukin-12 receptor beta2 chain on type 1 cytokine-stimulated T lymphocytes in type 1 diabetes.
An aberrant mitogen-induced polarization of peripheral blood T cells has been associated with type 1 diabetes (T1D). We studied, in T1D, type 1 and 2 cytokine-induced expression of the interleukin-12 receptor beta2 chain (IL-12Rbeta2 chain), which plays a critical role in regulating T-cell polarization. Peripheral blood lymphocytes from children with newly diagnosed T1D (n=10; mean age 10 years), from children with longstanding T1D (n=8; mean age 12.9 years) and from healthy children (n=15; mean age 11.5 years) were stimulated with phytohaemagglutinin (PHA) in a type 1 (IL-12 and anti-IL-4) or a type 2 (IL-4 and anti-IL-12) cytokine environment. Secretion of interferon-gamma (IFN-gamma), IL-5 and IL-13, as detected by enzyme-linked immunosorbent assay (ELISA), and expression of the IL-12Rbeta2 chain on CD4 and CD8 cells by flow cytometry, were analysed. Children with newly diagnosed and longstanding T1D had lower expression levels of the IL-12Rbeta2 chain on IL-12Rbeta2 chain-positive CD4 T cells (for a type 1 or a type 2 cytokine environment: P=0.01 and P=0.002 or P=0.02 and P=0.01, respectively) and on IL-12Rbeta2 chain-positive CD8 T cells (for a type 1 or a type 2 cytokine environment: P=0.007 and P=0.0007 or P=0.003 and P=0.01, respectively) when compared to healthy children. A decreased percentage of IL-12Rbeta2 chain-expressing CD4 T cells (P=0.07 and P=0.03) and CD8 T cells (P=0.004 and P=0.01) and increased secretion of IL-13 (P=0.006 and P=0.04) in a type 1 cytokine environment was seen in both groups of patients. Peripheral blood T cells from patients with both newly diagnosed and longstanding T1D showed poor polarization towards type 1 cells.
Skarsvik
Susanne
S
Division of Pediatrics, Department of Molecular and Clinical Medicine, Clinical Research Centre, Linköping University, Linköping, Sweden. Susanne.Skarsvik@imk.liu.se
Ludvigsson
Johnny
J
Vaarala
Outi
O
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D016764:Cell Polarity; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D053703:Interleukin-11 Receptor alpha Subunit; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000276:immunology*; D053702:Receptors, Interleukin-11; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D016207:Cytokines; C508428:IL11RA protein, human; D053703:Interleukin-11 Receptor alpha Subunit; D008934:Mitogens; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11