Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle

We previously reported that tumor necrosis factor alpha (TNF-α) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV). To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-α, we analyzed the mRNA expression levels for TNF-α in spontaneously proliferating PBMCs derived from BLV-infected cattle. The mean mRNA expression level for TNF-α was higher in the spontaneously proliferating PBMCs derived from BLV-infected cattle than in non-spontaneously proliferating PBMCs from normal cattle. The TNF-α protein level in the PBMCs was determined by flow cytometric analysis, and it was noted that most of the cells expressing membrane-bound TNF-α in the spontaneously proliferating cells were CD5+ or sIgM+-cells. Additionally, in order to determine if this spontaneous proliferation can be blocked by anti-bovine TNF-α MAb, the spontaneously proliferating PBMCs from a BLV-infected cattle were cultured in the presence of the MAb. The addition of this MAb at the beginning of the 72 h-cultivation clearly inhibited spontaneous proliferation of cells in a dose-dependent manner, indicating the direct involvement of TNF-α in the spontaneous proliferation of PBMCs during the late disease stage. These data suggest that an aberrant expression of TNF-α might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma.