HUMAN T-CELLS RECOVERED FROM HUMAN BALB RADIATION CHIMERAS ARE HYPERSENSITIVE TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION/

Replication of human immunodeficiency virus type 1 (HIV-1) is regulate d by virus-encoded regulatory proteins, as well as by a variety of cel lular factors. Productive infection of human T lymphocytes by HIV-1 is dependent upon the activation status of the target cells. In general, short-term mitogenic stimulation of CD4 T cells is used to enhance in fection of peripheral blood mononuclear cells (PBMC) in vitro. Recentl y, we demonstrated that adoptive transfer of human PBMC into lethally irradiated BALB/c mice, radioprotected with severe combined immunodefi ciency (SCID) mouse bone marrow, leads to marked T-cell activation and proliferation. In the present study, we investigated the effect of su ch xenoactivation of human T cells on their susceptibility to HIV-1 in fection. Human cells that were recovered from human/Balb radiation chi meras supported efficient replication of laboratory strains of HIV-1, as well as of HIV-1 clinical isolates. The multiplicity of infection r equired to attain effective virus replication in the recovered xenoact ivated human cells was 10- to 100-fold lower than that needed for infe ction of short- or long-term phytohemagglutinin (PHA)-stimulated blast s or of various T-cell lines. Analysis of human cell surface activatio n markers has indicated that xenoactivation in the mouse, in contrast to in vitro stimulation with PHA, is associated with a marked downregu lation of CD25 (interleukin 2 receptor). Our results demonstrate that human cells recovered from human/Balb radiation chimeras, which are hy persensitive to HIV-1 infection, differ from in vitro-stimulated cells in their activation status. Therefore, this system could be used to s tudy host factors that participate in HIV-1 infection and replication in vitro and in vivo.