Phenotypic and Ultrastructural Characteristics of Bronchoalveolar Lavage Cells of Lentivirus-Infected Lambs Treated with Recombinant Ovine IFN- τ

Abstract

Ovine lentivirus (OvLV) belongs to the family Retroviridae and closely resembles the human immunodeficiency virus (HIV). Pulmonary lesions in OvLV-infected sheep consist of lymphoid interstitial pneumonia(LIP) and lymphocytic alveolitis. Similar pulmonary lesions occur in up to 40% of HIV-infected children and in some adults with AIDS. Interferon-τ (IFN-τ), a type I IFN, is produced by trophectoderm of ruminant conceptuses and is the pregnancy recognition signal in these species. To evaluate changes in phenotypes of bronchoalveolar lavage (BAL) cells of OvLV-infected lambs treated with recombinant ovine IFN-τ (rOvIFN-τ), 24 lambs were randomly allocated to one of four groups (n = 6 per group): 1, no virus + placebo (NVP); 2, no virus + rOvIFN-τ(NVI); 3, virus + placebo (VP); 4, virus + rOvIFN-τ (VI). The BAL cells from 3 lambs in each group were labeled with monoclonal antibodies (mAb) to cell surface markers at 16 weeks of treatment, and cells from the remaining 3 lambs in each group were labeled with mAb at 34 weeks of treatment. After labeling, BAL cells were analyzed by flow cytometry. The morphology of BAL cells from all experimental lambs was examined by transmission electron microscopy (TEM). At week 16, no differences in the relative proportions of BAL cell phenotypes were detected among the experimental groups. At week 34, VI lambs had higher proportions of CD8⁺, γδ ⁺, MHC class II⁺, and L-selectin (LS⁺) BAL cells compared with VP lambs. Higher proportions of CD14⁺ and CD44⁺ cells were found in VP lambs compared with NVP lambs at 34 weeks. OvLV-like particles were detected only in bronchoalveolar macrophages of VP lambs. In this study, rOvIFN-τ increased the proportions of primary antiviral γδ ⁺ and CD8⁺ immune cells in OvLV-infected lambs. This may represent a cellular mechanism to explain the antiviral and therapeutic efficacy of this cytokine, in addition to its direct antiviral effect. However, because the actual number of cells labeled with mAb CD8 was low and some subsets of γδ cells may coexpress the CD8 marker, further studies are necessary to better define the role of rOvIFN-τ in the modulation of these cells in vivo.