EFFECTS OF CYCLOSPORINE-A ON OZONE-INDUCED PULMONARY LESION FORMATION- PHARMACOLOGICAL ELIMINATION OF THE T-LYMPHOCYTE REGULATORY RESPONSE

To assess the involvement of T-lymphocytes in ozone-induced lung damag e, CD-1 mice were exposed to air or 0.7 ppm ozone (1.37 mg O-3/m(3) ai r) in the presence and absence of the immunosuppressive drug cyclospor ine A (CSA). Mice were thus divided into four treatment groups for bot h the 4 and 14 day exposure times: 1) AIR + VEH, 2) AIR + CSA, 3) O-3 + VEH, and 4) O-3 + CSA. Thy-1.2 positive cells (T-lymphocytes) per pu lmonary lesion were determined and quantitative histomorphometric anal ysis of lesion volume was performed. By Day 14, the number of T-lympho cytes per lesion in O-3 + VEH (vehicle) animals had increased to appro ximately 3.5 times that seen at Day 4. At 4 and 14 days of O-3 + CSA t reatment, the number of T cells per lesion was half that seen in O-3 VEH mice. At Day 4, lesion size and appearance were comparable in O-3 + VEH and O-3 + CSA animals, while at Day 14, O-3 + CSA treatment res ulted in larger and more cellular lesions that contained a greater pro portion of polymorphonuclear cells, and the lesions extended further i nto the lung periphery. Inflammatory cells were observed in areas of e pithelial cell proliferation and in alveolar spaces distal to the smal l airway terminus. After 14 days, lesion volume was approximately twic e as great following O-3 + CSA administration than with O-3 treatment alone. These results are consistent with effects seen in another model of immunosuppression, the nude mouse, and they implicate a regulatory role for T-lymphocytes in the response to ozone.