Constrictive bronchiolitis obliterans (CBO) restricts long-term survival following lung transplantation. CBO may also develop following exposure to inhaled or systemic toxicants. A marker to detect early development of CBO via BAL or lung biopsy has not been elucidated. Our laboratory has created both transplant and toxicant CBO models in the rat with pathology replicating human disease. Early T-lymphocyte activation (Eta-1), a cytokine secreted by activated T-lymphocytes that recruits and activates pulmonary macrophages, was highly elevated early in our toxicant model but at nonsignificant levels in the mature transplant CBO model. We hypothesized that a T-cell subpopulation (gamma delta) would precede Eta-1 expression, thus would be an early marker of CBO.
Sequential sections of 4-6 wk samples of lung tissue from both models (n=12) were immunostained for Eta-1, total T cells (CD3), and gamma-delta T-cells. Lung areas of staining were quantified by morphometric means, intensity of staining, and cell counts in 20 high-power fields. Statistical analysis of the data groups was performed.
Eta-1 was elevated and widely present in the transplant model although the 4-week toxicant model showed limited staining. Transplant vs. toxicant CBO Eta-1 staining was significantly different, p=0.004. Gamma-delta T-cells were sparse in the largest perivascular lymph nodes, appearing throughout the lungs of both models. Their presence did not correlate with lung tissue osteopontin in sequential lung sections, however. Total T cell (CD3) counts showed an equal amount of perivascular inflammation in both models.
Differences in cytokine and T-cell staining suggest different pathophysiologic pathways in the development of toxicant vs. transplant-induced CBO. These data propose that T-cell subpopulation differences do not account for the significant difference in Eta-1 between the two models.
A marker of bronchial injury identifying progression could be of vast importance in the diagnosis of CBO. Further studies continue to uncover early immunologic markers of CBO.
Jennifer Svetlecic, None.