Context
Type 1 diabetes is a T cell-mediated autoimmune disease leading to the destruction of pancreatic islet ? cells. This disease is associated with numerous immunological abnormalities. A characteristic abnormality is decreased proliferation and altered cytokine production by T lymphocytes when exposed to TCR/CD3 agonists in vitro. This phenotype can be reversed by addition of costimulatory signals (eg combination of CD2/CD28 antibodies or exogenous cytokines), suggesting a constitutive defect in the TCR/CD3 signal transduction pathway. In T lymphocytes, TCR/CD3 engagement induces CD3?-chain phosphorylation by p56lck or p59fyn tyrosine kinases. CD3?-chain phosphorylation allows the docking and the phosphorylation of ZAP-70 tyrosine kinase, which in turn phosphorylates neighboring proteins such as linker for activation of T cells (LAT). After recruitment of various adaptor proteins, key effector enzymes such as phospholipase C ? (PLC-?) are activated. The authors studied TCR/CD3 transduction pathway in isolated T lymphocytes.