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M9480127.TXT
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1994-08-09
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Document 0127
DOCN M9480127
TI Human T cell lymphotropic virus type I-induced T cell activation.
Resistance to TGF-beta 1-induced suppression.
DT 9410
AU Hollsberg P; Ausubel LJ; Hafler DA; Center for Neurologic Diseases,
Brigham & Women's Hospital,; Boston, MA 02115.
SO J Immunol. 1994 Jul 15;153(2):566-73. Unique Identifier : AIDSLINE
MED/94292786
AB T cell proliferation is potently suppressed by TGF-beta during the G1
phase of the cell cycle. The mechanism appears to involve inhibition of
cell cycle kinases that phosphorylate the retinoblastoma protein (pRb),
a key regulator of cell cycle progression from G1 to S phase. Although
productive infection with the human T cell lymphotropic virus type I
(HTLV-I) induces T cell activation, it also, paradoxically, leads to
increased production of TGF-beta. To investigate whether infection by
HTLV-I conferred resistance to TGF-beta in non-immortalized T cells, we
generated T cell clones from patients with HTLV-I myelopathy by direct
single cell cloning. Here we report that HTLV-I-infected but not
uninfected T cell clones have hyperphosphorylated pRb consistent with
viral-induced T cell activation. Furthermore, the HTLV-I-infected T
cells were resistant to growth suppression by rTGF-beta 1 and this
correlated with the inability of TGF-beta 1 to prevent
hyperphosphorylation of pRb. However, when spontaneously proliferating
HTLV-I-infected T cell clones were further stimulated by cross-linking
of the CD3/TCR complex, the superimposed proliferation was significantly
inhibited by TGF-beta 1, suggesting that the TGF-beta 1 signaling
pathway was intact. Together these findings suggest that HTLV-I induces
T cell activation through a pathway that is insensitive to TGF-beta 1.
This may have implications for the altered immune regulation in patients
with HTLV-I myelopathy.
DE Base Sequence Human HTLV-I/*IMMUNOLOGY Lymphocyte
Transformation/*DRUG EFFECTS Molecular Sequence Data Phosphorylation
Retinoblastoma Protein/METABOLISM RNA, Messenger/ANALYSIS RNA,
Viral/ANALYSIS S Phase/DRUG EFFECTS Support, Non-U.S. Gov't Support,
U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY Transforming Growth
Factor beta/*PHARMACOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).