Transforming growth factors beta slow down cell-cycle progression in a murine interleukin-2 dependent T-cell line

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Abstract
Transforming growth factors beta (TGF-β) inhibit the growth of a variety of cell types, including lymphocytes. The immunosuppressive effects of TGF-β have been attributed to the interference of these molecules with the interleukin-2 (IL2)-driven component of lymphocyte proliferation. In order to elucidate in more detail the effects of TGF-β on IL-2-induced proliferation, we investigated the effects of porcine transforming growth factor beta 1 and 2 (pTGF-β1 and 2) on the IL-2-driven proliferation of a murine IL-2-dependent T-lymphocyte line (CTLL). The results showed that pTGF-β1 and 2 decreased 3H-thymidine incorporation in CTLL cells in a dose-dependent fashion (maximum decrease of 75–85%). Combined-time kinetic analysis of the effects of pTGF-β on 3H-thymidine incorporation, cell growth, and cell-cycle distribution (monitored as DNA content distribution) revealed that, in the first 48 h of culture, pTGF-β1 increased the doubling time from 11.4 to 19.2 h without significantly affecting the cell-cycle distribution of CTLL cells. After 96 h of culture in the presence of pTGF-β1, cells started to accumulate in G0/G1, although at this time point 30% of the pTGF-β1-treated cells were still in S-G2/M. Furthermore, during the first 48 h, neither the expression of the 55 kd chain of the IL-2 receptor (IL-2R) nor the expression of the transferrin receptor (TfR) was affected by TGF-β. After 72 h of culture in the presence of pTGF-β1, the expression of the IL-2R and TfR was decreased. The data suggest that in CTLL cells TGF-β initially slows the progression of cells in all phases of cell cycle. In addition, the initial TGF-β-mediated decrease of IL-2-induced 3H-thymidine incorporation and cell proliferation in CTLL cells is not due primarily to downregulation of the IL-2R and/or TfR.