γ/δ T cells contribute to inflammation following long term low dose O3 exposure. (120.32)

Abstract

Abstract γ/δ T cells are involved in the responses to acute high dose ozone (O3) exposure (2 ppm for 3 hrs)( Matsubara, S et al, AJRCMB, 2009). However, elevated atmospheric O3 tends to persist not for hours, but for several days. The factors that determine pulmonary responses to short-duration, high-dose O3 exposure are different from those involved in responses to longer, lower-dose exposures and it is not know what role γ/δ T cells have in these longer term exposures. Consequently, we exposed mice deficient in γ/δ T cells (TCRδ-/-) and WT mice to O3 (0.3 ppm for 48 hrs). Bronchoalveolar lavage (BAL) was performed and the lungs were collected, digested, and analyzed by FACS. O3 caused an increase in numbers of γ/δ T cells, macrophages, and neutrophils in the lung tissue and/or BAL fluid. BAL and lung tissue neutrophils and macrophages were reduced in TCRδ-/- versus WT mice. BAL fluid IP-10, IL-6, MCP-1, LIF and KC were lower in TCRδ-/- versus WT mice. These chemokines are chemoattractive for macrophages and/or neutrophils and most can be produced by lung γ/δ T cells. In contrast, we found no difference in O3 induced lung damage between the WT and TCRδ-/- mice, as assessed by BAL protein or scores of terminal bronchiolar lesions on histological sections. Our data indicate that γ/δ T cells are involved in the initiation of inflammation following O3 exposure, potentially through the secretion of chemokines that recruit macrophages and neutrophils.