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).