CD4 T lymphocyte activation in BLV-induced persistent B lymphocytosis in cattle

Bovine leukemia virus (BLV) is an oncogenic retrovirus in the human T cell leukemia virus family. BLV infects B lymphocytes and induces a nonmalignant persistent lymphocytosis (PL) and leukemia/lymphoma in cattle. There is ev idence that CD4 T lymphocytes are activated during BLV infection and promot e the development of FL. How CD4 T lymphocytes are activated by BLV infecti on is not known. We observed that CD4 T lymphocytes from PL cattle prolifer ated in the presence of autologous, irradiated peripheral blood mononuclear cells (PBMC), whereas no proliferation occurred in cell cultures from BLV- infected non-FL cattle. Proliferation required direct contact with metaboli cally active irradiated PBMC but was not associated with viral protein expr ession or inhibited by antibodies to BLV. Unexpectedly, B lymphocytes alone failed to account for the irradiated PBMC stimulation of CD4 T lymphocytes . These observations and the magnitude of the proliferative response sugges t that activation is polyclonal and involves mechanisms other than BLV anti gen-specific stimulation. (C) 2000 Academic Press.