Functional Characterization of T Cell Populations in a Mouse Model of Chronic Obstructive Pulmonary Disease

Abstract

Cigarette smoke (CS) exposure is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic peribronchial, perivascular and alveolar inflammation. The inflammatory cells consist primarily of macrophage, neutrophils and lymphocytes. Although myeloid cells are well studied, the role of lymphocyte populations in pathogenesis of COPD remains unclear. Using a mouse model of CS-induced emphysema our laboratory has previously demonstrated that CS exposure causes changes in the T cell receptor repertoire suggestive of an antigen specific response and triggers a pathogenic T cell response sufficient to cause alveolar destruction and inflammation. We extend these findings to demonstrate that T cells from CS-exposed mice of Balb/cJ or C57B6 strain are sufficient to transfer pulmonary pathology to CS-naïve, immunosufficient mice. CS exposure causes a proinflammatory phenotype among pulmonary T cells consistent with from COPD patients. We provide evidence that donor T cells from CS-exposed mice depend on antigen recognition to transfer alveolar destruction using MHC class I deficient recipient mice. Neither CD4+ nor CD8+ T cells from donor mice exposed to CS are alone sufficient to cause inflammation or pathology in recipient mice. We found no evidence of impaired suppression of T cell proliferation among regulatory T cells from CS-exposed mice. These results suggest that CS exposure initiates an antigen specific response that leads to pulmonary destruction and inflammation that involves both CD8+ and CD4+ T cells. These results are direct evidence for an autoimmune response initiated by CS exposure.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies

“…Both autoimmune mechanisms and IL-17 (31,(46)(47)(48)(49)(50)(51)(52)(53)(54) In an attempt to assess whether the altered microbiota in disease could directly enhance IL-17A responses, we performed a transfer experiment. Antibiotic treated mice were challenged with LPS/elastase on day 0,7 and 21.…”

Cigarette smoke represses the innate immune response to asbestos

“…To test this postulate, we exposed wild-type C57BL/6 (B6) mice 5 h per day to air or to CS (~150 mg/m 3 TSP) alone 4 days per week, and to asbestos (~20 mg/m 3 ) alone 1 day per week for 5 weeks. This level of whole body CS exposure, or less (90 mg/m 3 ), for 5 h/day, 5 days/week for 6 months is sufficient to induce emphysema in mice (Sussan et al 2009;Eppert et al 2013). The fourth group of mice received both CS plus asbestos by sequentially exposing them to CS and asbestos in a 2:1:2 (CS:asbestos:CS) daily format 5 days per week for 5 weeks as well ( Fig.…”

“…; Eppert et al. ). The fourth group of mice received both CS plus asbestos by sequentially exposing them to CS and asbestos in a 2:1:2 (CS:asbestos:CS) daily format 5 days per week for 5 weeks as well (Fig.…”

Timely Blockade of ICAM-1.LFA-1 Interaction Prevents Disease Onset in a Mouse Model of Emphysema

“…Emerging data from humans and mice suggest that the inflammation is a component of an autoimmune attack on lung tissue. Support for this is obtained by adoptive transfer of disease into naïve animals using T cells from mice with smoke-induced emphysema [2,3], and by observations that mice deficient in CD8 + T cells or MHC I fail to develop emphysema [2,4]. Additional support comes from observations of adaptive immune responses associated with emphysema [5][6][7][8] and the presence of oligoclonal T cells in emphysema patients [9,10].…”