Human immature thymocytes as target cells of the leukemogenic activity of
human T-cell leukemia virus type I
V Maguer-Satta, L Gazzolo and MD Dodon
Centre National de la Recherche Scientifique/Universite Claude Bernard,
Lyon, France.
The risk of developing adult T-cell leukemia (ATL) associated with neonatal
infection by human T-cell leukemia virus type I (HTLV-I) suggests that
early events triggered by HTLV-I might be of crucial importance in
initiating the multistep lymphoproliferative process leading several
decades later to the development of leukemic disease. Thus, infection of
thymocytes early in life might be directly correlated with the development
of ATL. In the present study, we show that in vitro infection of mature
(CD2+CD3+) or immature (CD2+CD3-) thymocytes resulted in the exogenous
interleukin (IL)-2-dependent proliferation of HTLV-I-positive thymocytes,
most of them displaying a CD2+CD3-CD4+ phenotype and expressing the CD25
molecule, the alpha chain of the IL-2 receptor. Furthermore, the CD80 and
CD54 antigens, normally expressed by thymic stromal cells, were detected on
these transformed thymocytes, indicating that HTLV-I infection may disturb
the cooperation between thymocytes and their thymic environment. These
HTLV-I-positive thymocytes were producing significant amounts of IL-6,
which was found to be implicated in their proliferation and in the
expression of CD25, as demonstrated by blocking experiments using a
monoclonal antibody to IL-6. The present study suggests that immature
thymocytes may provide an environment favorable to the unfolding of events
leading to leukemia.
Volume 86,
Issue 4,
pp. 1444-1452,
08/15/1995
Copyright © 1995 by The American Society of Hematology
