LATE-BREAKING ABSTRACT: T-cell membrane organization as a potential new target in asthma

Abstract

Introduction: In the context of antigen recognition, the crucial step driving lymphocyte proliferation is the signal transmission from antigen presenting cell (APC). This signaling involves both conformational change and clustering of T cell receptors (TCR) at the immunological synapse between lymphocyte and APC. Aim: Membrane cholesterol is of importance in TCR clustering and we hypothesized that a modification of T cell membrane lipid composition and fluidity could impair the signaling. Methods: To this end, we depleted cholesterol from T cell membrane by the use of cyclodextrins (2-HP-β-CD) to analyze the impact on membrane fluidity. We administered 2-HP-β-CD in vivo by inhalation in a mouse model of asthma (ova) and its ability to inhibit the lymphocyte proliferation and cytokine secretion was measured. Results: After 2-HP-β-CD incubation, T cell membrane fluidity was increased and their proliferation following TCR stimulation was significantly decreased. After 2-HP-β-CD treatment given by inhalation, mice exhibited significantly lower bronchial hyperresponsiveness, lower eosinophil counts in the BAL and less inflammation around the bronchi. The number of lymphocytes harvested from thoracic lymph nodes was decreased significantly. Conclusion: In this study, we demonstrate the interest of directly targeting lung T-cell membrane lipid composition to impair their activation following allergen presentation.