Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression
- PMID: 8021495
Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression
Abstract
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.
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