The discovery of EBV in certain T cell malignancies and the expression
of the EBV receptor, CR2/CD21, on a population of immature thymocytes
, T lymphoblastoid cell lines, and childhood acute T lymphoblastic leu
kemia cells suggested that EBV-receptor interactions on T cells may be
of importance. We have shown that, within the thymus, a population of
large, immature cells expresses CD21. EBV altered the activation resp
onses of immature thymocytes in vitro. Triggering through CD2 is mitog
enic for mature, but not immature, T cells. However, during infection
by EBV, ligation of CD2 caused thymocytes to proliferate in the absenc
e of exogenous cytokines. This function was a result of the interactio
n of EBV with its receptor, CD21, but was caused by infection rather t
han surface signaling, because neither specific mAb nor the P3HR-1 str
ain of virus mimicked the effect of B95-8. Immature thymocytes were in
fected by EBV, as determined by the internalization of the viral genom
e and its transcriptional activity. Consistent with the activity of B9
5-8, EBNA-2 transcripts were identified within infected thymocyte popu
lations. In addition, components of the viral replicative pathway were
expressed during infection of thymocytes. These components included t
ranscription of BZLF-1, an early gene that characterizes EBV-infected
B cells after disruption of latency. A second transcript was identifie
d as encoding the recently characterized RAZ, which also is associated
with replicative infection. The consequences of EBV infection of T ce
lls at an early stage of differentiation may lead to failure of normal
T cell repertoire development, autoimmunity, or malignancy.