Bm. Broker et al., IMMORTALIZATION OF HUMAN T-CELL CLONES BY HERPESVIRUS-SAIMIRI - SIGNAL-TRANSDUCTION ANALYSIS REVEALS FUNCTIONAL CD3, CD4, AND IL-2 RECEPTORS, The Journal of immunology, 151(3), 1993, pp. 1184-1192
Investigation of human activated T cells has been complicated by the n
eed for periodic restimulation with Ag/mitogen and accessory cells and
by the limited life span of most human T cell clones. To overcome the
se problems, we have transformed established human T cell clones to pe
rmanent growth with Herpesvirus saimiri, a lymphoma-inducing virus of
nonhuman primates. Three human CD4+ T cell clones were investigated in
detail. They have been growing in the presence of exogenous IL-2 but
without restimulation with mitogen or feeder cells for more than 11 mo
with doubling times between 2 and 4 days. In contrast, their nontrans
formed parent clones needed to be restimulated with PHA and feeder cel
ls every 14 to 21 days. To compare responses of H. saimiri-transformed
clones with those of their parent clones, we stimulated the cells wit
h IL-2 or with anti-CD3 and/or anti-CD4 mAb with and without cross-lin
king on the cell surface. Transformed and nontransformed T cell clones
were strikingly similar in parameters of early signal transduction, n
amely, tyrosine phosphorylation and mobilization of calcium. Ligation
of their TcR/CD3 complexes by mAb or by Ag in the presence of autologo
us accessory cells increased the proliferation and the secretion of IF
N-gamma. Taken together, we have shown that human T cell clones immort
alized with H. saimiri express functional CD3, CD4, and IL-2R. They co
nstitute a simple, stable, reproducible and accessory cell-free model
system for the investigation of signal transduction events in activate
d human T cells.