A Mechanism of T Cell Regulation of Epstein-Barr Virus Latency

The tumorigenic potential of B lymphocytes latently infected with EBV is effectively controlled by T cell immunity. The mechanisms of this T cell regulation, however, are incompletely understood. In this study. T lymphocytes were found to proliferate in response to serum-free supernatants of EBV-immortalized cells and to deplete them of growth factors required by the immortalized B cells for autocrine growth. Lactic acid was reported to account for approximately 90% of the autocrine growth activity in serum-free supernatants of EBV-immortalized cell lines. Synthetic lactic acid was now found to promote growth in activated T cells. In addition, B cell suppression resulting from coculture of EBV-infected B cells with autologous T cells was reversed by the addition of supernatants from EBV-immortalized cell lines. Thus, T cell competition for growth factors produced and utilized by EBV-immortalized B cells for continuous proliferation may represent an important and novel regulatory mechanism for the maintenance of EBV latency in B lymphocytes.