Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients

General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes

“…In general, T1D children, around the time of diagnosis, showed a low spontaneous secretion of all the studied cytokines (IL-6, IL-10, IL-13, IL-17, IFN-γ, and TNF-α) in comparison to healthy children. This is in accordance with the decreased Th1 immunology at T1D onset, which we and others have reported previously (14,15,18,19). It could be speculated that the low, seemingly suppressed, spontaneous cytokine secretions could be an effect of exhaustion of the immune system following the strong immune activation preceding the onset and diagnosis of T1D.…”

“…In contrast, children with a prolonged duration of symptoms prior to diagnosis showed a Th2-like (IL-13) and a Tr1-like (IL-10) immune activity that may implicate a less aggressive autoimmune attack. We have previously shown that still-healthy individuals with a high risk of developing the disease have a Th2-prone immune profile in response to diabetes-associated autoantigens (14,18). This Th2/Tr1-like immune response may favor survival of β cells and thus delays the onset of disease.…”

“…Also, IL-17 immunity has been suggested in human T1D due to the findings of increased secretion and expression of IL-17, as well as an increased proportion of IL-17-secreting cells (12). In contrast, Th2-like cytokines, e.g., IL-4, IL-5, and IL-13 have been shown to be downregulated during this organ-specific autoimmune process (13)(14)(15). In addition, IL-10 secreted from regulatory T cells (Tr1), and transforming growth factor-β secreted by Th3 cells, inhibits Th1 cytokine synthesis (16).…”

CD4 T cell differentiation in type 1 diabetes

“…A separate analysis concluded that T cells from people with T1D produced equivalent amounts of IFN-g and IL-13 in response to autoantigens as T cells from control subjects [42]. Regarding the prediabetic period, the Th1 response to autoantigen has been reported to be increased in one study [43] and decreased in another [44] in at-risk individuals. One must be mindful when assaying peripheral blood that a lower response could potentially signify the migration of disease-relevant T cells to the pancreas.…”

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

“…Proinflammatory cytokines such as IL-1β, IFN-γ and TNF-α promote the destruction of pancreatic beta cells [3][4][5], while regulatory cytokines (IL-10 and TGF-β 1 ) [6,7] and anti-inflammatory cytokines (IL-1 receptor antagonist [IL-1RA]) [8] can counteract beta cell destruction. An imbalance between pro-and anti-inflammatory and/or regulatory cytokines could be essential for the development of type 1 diabetes [9][10][11].…”