Aberrant regulation of interleukin-12 receptor β2 chain on type 1 cytokine-stimulated T lymphocytes in type 1 diabetes

Abstract

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 β2 chain (IL-12Rβ2 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-γ (IFN-γ), IL-5 and IL-13, as detected by enzyme-linked immunosorbent assay (ELISA), and expression of the IL-12Rβ2 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-12Rβ2 chain on IL- 12Rβ2 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-12Rβ2 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-12Rβ2 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.