2135-LB: The Study of Abnormal SLAMF Molecular Expression on Immune Cells in Type 1 Diabetic Patients and Associated Mechanism

Introduction and Objective: At present, the pathogenesis of T1DM is not completely clear, and more and more studies have shown that CD8+T cells play an important role in the pathogenesis of type 1 diabetes. It has been reported that the signaling lymphocyte activated molecular family (SLAMF) is abnormally expressed in various immune disorders and affects the differentiation and function of immune cells. However, the expression of SLAMF molecules on the immune cell surface of T1DM has not been reported, and it is still unclear how SLAM molecules affect the function of CD8+T cells in T1DM. Methods: We measured the frequencies of immune cells and SLAMF molecules expression on the surface of immune cells. The expression of SLAMF4 molecule and the secretion of pro-inflammatory cytokines and cell activation status were detected. The expression of SLAMF4 molecules on PBMC were detected by flow cytometry.(4) SLAMF4+CD8+T cells and SLAMF4-CD8+T cells of T1DM patients mRNA and mice transcriptome was sequenced to analyzed. Results: (1)Compared with HCs, the percentage of SLAMF4-positive CD8+T cells in T1DM patients decreased significantly, and the expression and activation of SLAMF4 molecules were related to the secretion of pro-inflammatory cytokines (2) The expression of SLAMF4 molecule is significantly related to the apoptosis of CD8+T cells in patients with T1DM. SLAMF4 positive CD8+T cells have poor proliferation ability and are more prone to apoptosis, so the percentage of SLAMF4 positive CD8+T cells will decrease after sustained antigen stimulation in vivo. Conclusion: This investigation analyzed the expression profile of SLAMF molecule family in T1DM disease model for the first time, which provided experimental evidence for the regulation between SLAMF molecule and immune cells. We also confirmed the change of SLAMF4 positive CD8+T cells proportion in T1DM immune microenvironment and suggested that SLAMF4 molecule might provide a new target for early diagnosis, clinical staging or immune intervention of T1DM. Disclosure L. Sun: None.