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Abstract Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by insulin insufficiency that results from a progressive immunological destruction of insulin-secreting pancreatic islet ?-cells by autoreactive leukocytes and their mediators. IDDM is associated with altered humoral and cellular immunity. Both CD4+ T cells and CD8+ T cells have been implicated in the pathogenesis of IDDM. In parallel with these effector cells, other regulatory T cells that can block the development of IDDM include CD4+CD62L+ thymocytes, CD4+CD25+ splenocytes ,and Natural killer T cells. Natural Killer T (NKT) cells are a unique subset of T cells that coexpress receptors of the NK lineage and ?? T cell receptor. Most NKT cells express an invariant TCR ? chain encoded by the V?14-J?281 gene segment, paired preferentially to V?8, V?7, and V?2 chain. Type 1 diabetes is strongly genetically linked and associated with human leukocyte antigen (HLA) on chromosome 6 which contains multiple susceptibility alleles DR and DQ of the HLA class II genes. HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecule (class Ib) structurally related to classical MHC class Ia (HLA-A, -B, -C) that in contrast to class Ia molecules exhibits a limited tissue distribution, characterized by a limited polymorphism. This study included 28 patients with IDDM. They comprised 15 females and 13 males with age range from 1.5 to 15 years. patients were classified into recent onset group (< 1 month duration) and old or established cases who had longer disease duration. All patients and controls were subjected to thorough history, clinical examination, random blood sugar and glycosylated hemoglobin assessment. In addition, blood samples were withdrawn aseptically for NKT cells isolation, assessment of NKT cell receptor V?24-J?Q by ELISA before and after mitogen stimulation and by PCR. Assessment of soluble HLA-G by ELISA and HLA-G expression by PCR were also done. After statistical analysis of the data we reached the following results: 1- NKT cells frequency and activity are reduced in children with IDDM that may denote a role for these cells in disease pathogenesis. 2- HLA-G level and expression are increased in children with IDDM suggesting a role in disease pathogenesis. 3- Studied variables, namely NKT cells and HLA-G didn’t vary with age, duration of illness, or state of disease control. |