Transforming growth factors beta slow down cell-cycle progression in a murine interleukin-2 dependent T-cell line
✍ Scribed by Michael Stoeck; Sylvia Miescher; H. Robson MacDonald; Vladimir Von Fliedner
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 883 KB
- Volume
- 141
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Transforming growth factors beta (TGF-P) inhibit the growth of a variety of cell types, including lymphocytes. The immunosuppressive effects of TGF-P have been attributed to the interference of these molecules with the interleukin-2 (IL-2)-driven component of lymphocyte proliferation. In order to elucidate in more detail the effects of TGF-P on IL-2-induced proliferation, we investigated the effects of porcine transforming growth factor beta 1 and 2 (pTGF-Pl and 2) on the IL-2-driven proliferation of a murine IL-2-dependent T-lymphocyte line (CTLL). The results showed that pTGF-Pl and 2 decreased 'H-thymidine incorporation in CTLL cells in a dose-dependent fashion (maximum decrease of 75-85%). Combined-time kinetic analysis of the effects of pTGF-P on 'H-thymidine incorporation, cell growth, and cell-cycle distribution (monitored as DNA content distribution) revealed that, in the first 48 h of culture, pTGF-Pl increased the doubling time from 1 1.4 to 19.2 h without significantly affecting the cell-cycle distribution of CTLL cells. After 96 h of culture in the presence of pTGF-PI, cells started to accumulate in COiC1, although at this time point 30% of the pTGF-pl-treated cells were still in S-CZ/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-P. After 72 h of culture in the presence of pTGF-Pl, the expression of the IL-2R and TfR was decreased. The data suggest that in CTLL cells TGF-P initially slows the progression of cells in all phases of cell cycle. In addition, the initial TGF-P-mediated decrease of IL-2induced 'H-thymidine incorporation and cell proliferation in CTLL cells is not due primarily to downregulation of the IL-2R and/or TfR.