T-cell activation and HLA-regulated response to smoking in the deep airways of patients with multiple sclerosis

•Smokers show increased proliferation of T-cells in the lung.•MS-patients display increased preformed CD40L in pulmonary CD4+ T-cells.•Disease modifying treatment in MS does not alter cellular distribution in the lung.•Increase of alveolar macrophages is associated with smoking status and HLA-alleles.

Cigarette smoking is a risk factor for multiple sclerosis (MS), and the risk is further multiplied for HLA-DRB1*15+ smokers. To define the smoke-induced immune responses in the lung we performed bronchoscopy with bronchoalveolar lavage (BAL) on smokers and non-smokers, both MS-patients and healthy volunteers. In the BAL, non-smokers with MS showed an increased preformed CD40L expression in CD4 + T-cells while smokers displayed an increase in proliferating (Ki-67+) T-cells. In addition, our results confirm that smoking induces an increase of alveolar macrophages in BAL, and further defined a significant attenuation of this response in carriers of the HLA-DRB1*15 allele, in both MS patients and healthy controls. This first systematic investigation of the immune response in the lungs of smokers and non-smokers diagnosed with MS, thus suggests an MS-associated lung T-cell phenotype, involvement of a specific T-cell response to smoke, and a genetic regulation of the macrophage response.