Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division.
Growth factors have been defined by their ability to promote the proliferative expansion of receptor-bearing cells. For example, antigen-activated T cells expressing the alpha beta gamma form of the interleukin 2 (IL-2) receptor will proliferate in response to IL-2. In contrast, resting T cells, which express the IL-2 receptor beta and gamma chains, do not proliferate in response to IL-2. We demonstrate that the survival of resting T cells following gamma irradiation is greatly enhanced by pretreatment with IL-2. The radioprotective effect of IL-2 is dose dependent, does not result from the induction of cell proliferation, and does not require expression of the IL-2 receptor alpha chain. Thus, the beta gamma IL-2 receptor expressed on resting T cells can transduce signals that promote cell survival without committing the T cell to undergo cell division. IL-4 and IL-7, but not IL-1, IL-3, or IL-6, were also found to enhance the survival of quiescent T cells following gamma irradiation. Thus, certain growth factor-receptor interactions can serve to maintain cell viability in a manner that is independent of their ability to initiate or maintain cell proliferation. These data may have important implications for the use of growth factors in patients being treated with radiation and/or chemotherapy.
Boise
L H
LH
Gwen Knapp Center, Howard Hughes Medical Institute, University of Chicago, IL 60637, USA.
Minn
A J
AJ
June
C H
CH
Lindsten
T
T
Thompson
C B
CB
D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D005720:Gamma Rays; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein