Chronic cigarette smoke exposure generates pathogenic T cells capable of driving COPD-like disease in Rag2-/- mice

Am J Respir Crit Care Med. 2010 Jun 1;181(11):1223-33. doi: 10.1164/rccm.200910-1485OC. Epub 2010 Feb 4.


Rationale: Pathogenic T cells drive, or sustain, a number of inflammatory diseases. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with the accumulation of activated T cells. We previously demonstrated that chronic cigarette smoke (CS) exposure causes oligoclonal expansion of lung CD4(+) T cells and CD8(+) T cells in a mouse model of COPD, thus implicating these cells in disease pathogenesis.

Objectives: To determine whether T cells are pathogenic in a CS-induced mouse model of COPD.

Methods: We transferred lung CD3(+) T cells from filtered air (FA)- and CS-exposed mice into Rag2(-/-) recipients. Endpoints associated with the COPD phenotype were then measured.

Measurements and main results: Here, we demonstrate that chronic CS exposure generates pathogenic T cells. Transfer of CD3(+) T cells from the lungs of CS-exposed mice into Rag2(-/-) recipients led to substantial pulmonary changes pathognomonic of COPD. These changes included monocyte/macrophage and neutrophil accumulation, increased expression of cytokines and chemokines, activation of proteases, apoptosis of alveolar epithelial cells, matrix degradation, and airspace enlargement reminiscent of emphysema.

Conclusions: These data formally demonstrate, for the first time, that chronic CS exposure leads to the generation of pathogenic T cells capable of inducing COPD-like disease in Rag2(-/-) mice. This report provides novel insights into COPD pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bronchoalveolar Lavage Fluid / cytology
  • CD3 Complex / immunology
  • Cathepsins / metabolism
  • Cells, Cultured
  • Chemokines / metabolism
  • Cytokines / metabolism
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Epithelial Cells / pathology
  • Female
  • Leukocytes / metabolism
  • Lung / pathology
  • Macrophages / metabolism
  • Matrix Metalloproteinase 12 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Alveoli / pathology
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / pathology
  • T-Lymphocytes / metabolism
  • Tobacco Smoke Pollution / adverse effects*


  • CD3 Complex
  • Chemokines
  • Cytokines
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Tobacco Smoke Pollution
  • Cathepsins
  • cathepsin S
  • Matrix Metalloproteinase 12