OC 05.5 - Increased levels of glycolysis in CD4+ T cells of patients with Immune Thrombocytopenia

Background: Glycolysis is a vital metabolic pathway essential for T cell activation, exerting a central role in regulating diverse physiological processes. Abnormalities in CD4+ T cells, encompassing activation, polarization shift, and regulatory T cells (Treg) deficiency, are implicated in the pathogenesis of immune thrombocytopenia (ITP). Nevertheless, the association of these abnormalities with glycolysis in CD4+ T cells from patient with ITP is not fully understood.

Aims: This study aims to elucidate the aberrant glycolytic metabolism in CD4+ T cells of patients with ITP and clarify its regulatory role in CD4+ T cell function.

Methods: A total of 93 patients and 45 healthy controls were enrolled in the study. Flow cytometry was employed to assess 2-NBDG uptake and expressions of glycolysis-related enzymes(GLUT1, LDHA, PKM2, HK2, and PFKPB3). Furthermore, the study assessed the influence of glycolysis modulation through 2-DG or varied glucose concentrations in culture media on CD4+ T cell proliferation, activation, and the differentiation of Treg.

Results: CD4+ T cells from patients with ITP exhibited elevated glucose uptake, even after resting or reactivation compared to healthy controls. Treatment with glucocorticoids downregulated the glucose uptake capacity of CD4+ T cells. Additionally, GLUT1 expression on CD4+ T cells from ITP patients was significantly increased. The addition of the GLUT1 inhibitor 2-DG led to a notable reduction in glucose uptake and lactate production, coupled with suppressed proliferation and activation of CD4+ T cells. Culturing ITP CD4+ T cells in a low-glucose environment yielded results similar to 2-DG treatment, and partial restoration of Treg deficiency in patients with ITP.

Conclusion(s): CD4+ T cells from patients with ITP exhibit increased glycolytic metabolism, potentially contributing to their hyperactivation and skewed differentiation. Modulating glycolysis could be a promising therapeutic approach for treating ITP.