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

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.