Transforming growth factors beta slow down cell-cycle progression in a murine interleukin-2 dependent T-cell line.
Transforming growth factors beta (TGF-beta) inhibit the growth of a variety of cell types, including lymphocytes. The immunosuppressive effects of TGF-beta 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-beta on IL-2-induced proliferation, we investigated the effects of porcine transforming growth factor beta 1 and 2 (pTGF-beta 1 and 2) on the IL-2-driven proliferation of a murine IL-2-dependent T-lymphocyte line (CTLL). The results showed that pTGF-beta 1 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-beta 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-beta 1 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-beta 1, cells started to accumulate in G0/G1, although at this time point 30% of the pTGF-beta 1-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-beta. After 72 h of culture in the presence of pTGF-beta 1, the expression of the IL-2R and TfR was decreased. The data suggest that in CTLL cells TGF-beta initially slows the progression of cells in all phases of cell cycle. In addition, the initial TGF-beta-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.
Stoeck
M
M
Ludwig Institute for Cancer Research, Epalinges, Switzerland.
Miescher
S
S
MacDonald
H R
HR
Von Fliedner
V
V
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D013997:Time Factors; D015291:Transforming Growth Factors / Q000494:pharmacology*
D000954:Antigens, Surface; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D015291:Transforming Growth Factors; D004247:DNA