CD4 + T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

Abstract

ABSTRACT In immunodeficient hosts, Epstein-Barr virus (EBV) often induces extensive B-cell lymphoproliferative disease and lymphoma. Without effective in vitro immune surveillance, B cells infected by the virus readily form immortalized cell lines. In the regression assay, memory T cells inhibit the formation of foci of EBV-transformed B cells that follows recent in vitro infection by EBV. No one has yet addressed which T cell regulates the early proliferative phase of B cells newly infected by EBV. Using new quantitative methods, we analyzed T-cell surveillance of EBV-mediated B-cell proliferation. We found that CD4 + T cells play a significant role in limiting proliferation of newly infected, activated CD23 + B cells. In the absence of T cells, EBV-infected CD23 + B cells divided rapidly during the first 3 weeks after infection. Removal of CD4 + but not CD8 + T cells also abrogated immune control. Purified CD4 + T cells eliminated outgrowth when added to EBV-infected B cells. Thus, unlike the killing of EBV-infected lymphoblastoid cell lines, in which CD8 + cytolytic T cells play an essential role, prevention of early-phase EBV-induced B-cell proliferation requires CD4 + effector T cells.