Mitochondrial alterations in T cells after invivo and invitro smoke exposure

Introduction: T cell dysfunction may contribute to increased susceptibility to infections and disease progression in patients with chronic obstructive pulmonary disease (COPD). Mitochondria coordinate T cell activation, proliferation and differentiation and may be affected by hyperinflammation in COPD or direct smoke-induced toxicity. We thus investigated mitochondrial function of T cells after in vivo and in vitro smoke exposure. Methods: Gene expression, mitochondrial respiration and T cell phenotype were investigated in T cells isolated from mice after 2 weeks or 3 months of in vivo cigarette smoke exposure by microarray analysis, respirometry, and flow cytometry respectively. In vitro, naïve and activated T cells were treated with cigarette smoke extract (CSE). Mitochondrial respiration, as well as T cell activation/differentiation were determined by respirometry and flow cytometry respectively. Results: In vivo smoke exposure increased expression of genes related to the electron transport chain, Krebs cycle and pro-inflammatory cytokines in spleen T cells isolated from mice exposed to cigarette smoke. Accordingly, mitochondrial respiration was increased in spleen T cells after smoke exposure. Moreover, in vivo smoke exposure increased lung infiltration by effector CD4+ and CD8+ T cells, as well as activation of CD8+ T cells. In contrast, in vitro CSE exposure of isolated spleen T cells for 3 and 24 hours decreased mitochondrial respiration, as well as T cell activation. Conclusions: Smoke-induced effects on mitochondria of T cells differ between in vivo and in vitro smoke exposure, indicating activation of mitochondria and T cells by in vivo smoke exposure but inhibitory effects of in vitro smoke exposure. Funded by the German Research Foundation (KFO 309, Project 10)