TY - JOUR
T1 - Mechanism of T cell proliferation in vivo
T2 - analysis of IL-2 receptor expression and activation of c-myc and c-myb oncogenes during lymphatic regeneration
AU - Sihvola, M
AU - Sistonen, L
AU - Alitalo, K
AU - Hurme, M
PY - 1989/4/14
Y1 - 1989/4/14
N2 - The mechanism of T cell proliferation was studied using in vivo lymphatic regeneration as the model. Lymphatic regeneration was induced by injecting a sublethal dose (300 mg/kg) of cyclophosphamide (Cy) into mice. Majority of the regenerating splenic T cells were found to be in the cell cycle, nearly 30% being found in S/G2+M phases resembling the ratio obtained for mitogen activated T cells in vitro. Expression of interleukin-2 receptor (IL-2R) was defined by the monoclonal anti-IL-2R antibody, AMT-13. Only 1-3% of regenerating T cells were IL-2R positive (while about 30% of the in vitro activated T cells were IL-2R positive). Accordingly, these cells did not respond to IL-2 in vitro. However, when the freshly isolated regenerating T cells were cultured in the presence of Con A or PMA + ionophore A 23187, IL-2R was readily induced. The regenerating T cells were further analyzed for the expression of the cellular oncogenes c-myc and c-myb. These cells expressed about three times more c-myb mRNA than Con A-stimulated T cells and the levels were comparable to those seen in thymocytes. By contrast, the amount of c-myc mRNA was similar in the regenerating T cells and in Con A-activated T cells, but weak or barely detectable in splenocytes and thymocytes. Taken together, our results imply that the vigorous T cell proliferation during cyclophosphamide-induced lymphatic regeneration is independent of the IL-2/IL-2R hormone system, like T-cell precursor proliferation in the thymus, and is characterized by both high c-myb expression typical for thymocytes and high c-myc expression typical for in vitro proliferation-activated T cells.
AB - The mechanism of T cell proliferation was studied using in vivo lymphatic regeneration as the model. Lymphatic regeneration was induced by injecting a sublethal dose (300 mg/kg) of cyclophosphamide (Cy) into mice. Majority of the regenerating splenic T cells were found to be in the cell cycle, nearly 30% being found in S/G2+M phases resembling the ratio obtained for mitogen activated T cells in vitro. Expression of interleukin-2 receptor (IL-2R) was defined by the monoclonal anti-IL-2R antibody, AMT-13. Only 1-3% of regenerating T cells were IL-2R positive (while about 30% of the in vitro activated T cells were IL-2R positive). Accordingly, these cells did not respond to IL-2 in vitro. However, when the freshly isolated regenerating T cells were cultured in the presence of Con A or PMA + ionophore A 23187, IL-2R was readily induced. The regenerating T cells were further analyzed for the expression of the cellular oncogenes c-myc and c-myb. These cells expressed about three times more c-myb mRNA than Con A-stimulated T cells and the levels were comparable to those seen in thymocytes. By contrast, the amount of c-myc mRNA was similar in the regenerating T cells and in Con A-activated T cells, but weak or barely detectable in splenocytes and thymocytes. Taken together, our results imply that the vigorous T cell proliferation during cyclophosphamide-induced lymphatic regeneration is independent of the IL-2/IL-2R hormone system, like T-cell precursor proliferation in the thymus, and is characterized by both high c-myb expression typical for thymocytes and high c-myc expression typical for in vitro proliferation-activated T cells.
KW - Animals
KW - Calcimycin/pharmacology
KW - Cell Division
KW - Concanavalin A/pharmacology
KW - Cyclophosphamide/pharmacology
KW - Gene Expression Regulation
KW - Lymphatic System/physiology
KW - Lymphocyte Activation/drug effects
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Inbred CBA
KW - Proto-Oncogene Proteins/genetics
KW - Proto-Oncogene Proteins c-myb
KW - Proto-Oncogene Proteins c-myc
KW - Proto-Oncogenes
KW - Receptors, Interleukin-2/biosynthesis
KW - Regeneration/drug effects
KW - T-Lymphocytes/cytology
KW - Tetradecanoylphorbol Acetate/pharmacology
U2 - 10.1016/0006-291x(89)91638-0
DO - 10.1016/0006-291x(89)91638-0
M3 - Article
C2 - 2496686
SN - 0006-291X
VL - 160
SP - 181
EP - 188
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -