Type 1 diabetes is a T cell mediated autoimmune disease, often presented in children.Development of T1D is a chronic progression, wherein memory CD4 + T cells (CD4 + Tm)are believed to play a pivotal role in mediating autoimmune responses. It has been proposed that dysfunction in effector memory cells may contribute to autoimmunity in T1D.Using a unique cohort of age-and gender-matched children with T1D, their non-diabetic siblings and unrelated healthy control children, we undertook a detailed immunological study, including circulating CD4 + Tm cell counts, and activation, proliferation, effector responses and apoptosis in reactivated CD4 + Tm cells during TCR stimulation induced by anti-CD3/anti-CD28 mAb.We found T1D was associated with a reduced circulating CD4 + Tm cell count, and a similar reduction in circulating CD4 + Tm cells was also evident in the siblings. In both children with
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CD8+ T cell lineages) as well as in response to islet-specific antigen challenge is warranted in further studies. Nonetheless, this study provides new insights for further defining mechanisms underlying T1D pathophysiology, and illuminates specific immune cell lineages, biologically relevant surface receptors, cytokines, and biochemical pathways for therapeutic targeting.4