CD4+ T-cell effecters inhibit Epstein-Barr virus-induced B-cell proliferation

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-tell 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.