Infection with human T-lymphotropic viruses leads to constitutive
expression of leukemia inhibitory factor and interleukin-6
RB Lal, D Rudolph, C Buckner, D Pardi and WC Hooper
Retrovirus Diseases Branch, National Center for Infectious Diseases,
Centers for Disease Control, Atlanta, GA 30333.
Leukemia inhibitory factor (LIF), similar to interleukin-6 (IL-6), is a
glycoprotein growth factor and differentiation regulator that has
pleiotropic activity in several cellular systems. Recent reports of
constitutive IL-6 production from spontaneously proliferating cells from
human T-cell leukemia virus (HTLV)-infected individuals led us to examine
the expression of IL-6 and LIF during HTLV infection. In vitro infection of
peripheral blood lymphocytes with HTLV-I was associated with production of
both soluble LIF and IL-6 in conjunction with the increasing HTLV antigen
concentration. Northern blot analysis of T-cell lines generated from
individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II
(Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression
of LIF and IL-6 transcripts, as compared with uninfected cell lines
(HuT-78, Jurkat). The constitutive expression of LIF and IL-6 was
independent of presence of IL-2 in the culture medium, as both
IL-2-independent (MT-2, HuT-102, SP, Mo-T) and IL-2-dependent (FS, EG, H2A,
H2E) cell lines expressed LIF and IL-6 transcripts. Furthermore, LIF and
IL-6 RNA expression in an HTLV-I- infected cell line (MT-2) was enhanced by
phorbol ester stimulation via mechanisms that appear to be dependent on the
posttranscriptional regulatory controls. These results show that both LIF
and IL-6 are produced by HTLV-I- and HTLV-II-infected cells, which could
potentially alter the transcriptional regulation of HTLV gene expression by
inducing certain early response genes.
Volume 81,
Issue 7,
pp. 1827-1832,
04/01/1993
Copyright © 1993 by The American Society of Hematology