Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes

Epstein-Barr Virus is associated with several neoplasms in man. It is presumed to be the causative agent of infectious mononucleosis (1), a self-limiting lymphoproliferative disease, and is consistently associated with nasopharyngeal carcinoma (NPC) (2) ~ and African Burkitt's lymphoma (BL) (3). Viral isolates from the throat washings of patients with infectious mononucleosis can transform normal human lymphocytes in vitro giving rise to lymphoblastoid cell lines which express the Epstein-Barr (EB) nuclear antigen, carry multiple copies of the viral genome, and are of B-cell origin (4-6). Transforming Epstein-Barr virus (EBV) may also be used to induce lymphomas in marmosets from which virus-producing lymphoblastoid cell lines may be established (7). One such line, B95-8, has been used extensively as a source of transforming EBV (8). Little is known about the mechanism by which EBV infects B lymphocytes, how the lymphoproliferation typical of infectious mononucleosis is controlled, and the nature of the breakdown in these controls during NPC and BL. A role of humoral immunity is protection against reinfection is suggested by the persistance of anti-EBV neutralizing titers after EBV infection (9). The possibility of cellular immunity during the acute phase of infectious mononucleosis (IM) has been suggested by the presence of cytotoxic cells specific for EBV-carrying cell lines (10); however, the levels of killing reported are variable. After recovery from IM the viral infection is not completely eliminated but is carried in some latent or suppressed form, as healthy seropositive individuals appear to carry infected cells at a very low number. These cells must exist because outgrowth of EBV-positive lymphoblastoid cell lines may be achieved from the lymphocytes of seropositive individuals without the addition of exogenous virus. In vitro culture of fetal cord lymphocytes or lymphocytes from seronegative donors does not result in such an outgrowth (11).