A comparison of steady-state levels of IL-2 mRNA from activated T cells of IDDMs and age-matched controls, however, demonstrated lower levels of IL-2 mRNA in IDDMs compared to controls.
In vivo-activated interleukin 2 receptor-positive T lymphocytes (Tac cells) are demonstrable and the autologous mixed leukocyte reaction (AMLR) is impaired in several autoimmune diseases, including type 1 insulin-dependent diabetes mellitus (IDDM).
Twins with Type I diabetes had decreased interleukin-2 production as compared with normal controls (33.2 +/- 5.4 vs. 61.6 +/- 4.6 percent, P less than 0.001) and with their nondiabetic twins (33.2 +/- 5.4 vs. 54.5 +/- 3.4 percent, P less than 0.005).
Blood T-cells from 28 patients with type I (insulin-dependent) diabetes (IDDM) of variable duration were examined for the Tac antigen by immunofluorescence, and for proliferation in the presence of interleukin 2 (IL 2).
Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes.
Functional genetic polymorphisms of proinflammatory (T-helper-1: IL-2, IL-12 and IFN-gamma), anti-inflammatory (T-helper-2: IL-4, IL-6 and IL-10) and metabolic (IGF-I, VDR and INS) genes were determined in 206 Dutch simplex families with juvenile onset T1D and the results were analysed using the transmission disequilibrium test.
As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex.
This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis).
The non-redundant role of IL-2 and its receptor in etiology of T1D could be particularly attributable to the regulation of CD4+ CD25+ regulatory T cells, whose function is critical in maintaining immune homeostasis.
Commonality in the genetic control of Type 1 diabetes in humans and NOD mice: variants of genes in the IL-2 pathway are associated with autoimmune diabetes in both species.
Higher IFN-gamma and IL-2 response to enterovirus in children with HLA class II protective haplotype DR2-DQ6 could be of importance in the protection from T1D-associated enterovirus infections.
In addition, IL2RA genetic variants correlate with the levels of a soluble form of the IL-2 receptor in subjects with type 1 diabetes and multiple sclerosis.
Polymorphisms within the IL2-IL21 linkage disequilibrium (LD) block show a novel association with IBD, this is concordant with suggestive previous results of whole genome analyses in CD and type 1 diabetes.
Polymorphisms from the TENR-IL2-IL21 block in the 4q27 chromosome were recently associated with type 1 diabetes, celiac disease, rheumatoid arthritis and psoriasis.
Further, expression signatures and increased apoptosis in T(regs) from T1D subjects partially mirrored the response of healthy T(regs) under conditions of IL-2 deprivation.
Here we use polychromatic flow cytometry to show that differences in surface expression of the human interleukin-2 (IL-2) receptor alpha (IL2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated with two autoimmune diseases, type 1 diabetes (T1D) and multiple sclerosis.
Previous studies suggested the association of interleukin-2 (IL2) gene polymorphisms and its alpha- and beta-chain receptor (IL2RA and IL2RB) variants with different autoimmune diseases such as T1D, celiac disease, multiple sclerosis, and rheumatoid arthritis.
This activity results in the identification of a series of potentially novel therapeutic targets that could restore proper immune regulation in type 1 diabetes by augmenting the IL-2 pathway.
The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10⁻⁶ and 2.5 × 10⁻⁵, respectively).
Children of parents with type 1 diabetes and prospectively followed from birth for the development of islet autoantibodies and diabetes were genotyped for single-nucleotide polymorphisms at 12 type 1 diabetes susceptibility genes (ERBB3, PTPN2, IFIH1, PTPN22, KIAA0350, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10 and COBL).