Abstract
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.
Original language | English |
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Pages (from-to) | 181-8 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 160 |
Issue number | 1 |
DOIs | |
Publication status | Published - 14 Apr 1989 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Animals
- Calcimycin/pharmacology
- Cell Division
- Concanavalin A/pharmacology
- Cyclophosphamide/pharmacology
- Gene Expression Regulation
- Lymphatic System/physiology
- Lymphocyte Activation/drug effects
- Mice
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins c-myb
- Proto-Oncogene Proteins c-myc
- Proto-Oncogenes
- Receptors, Interleukin-2/biosynthesis
- Regeneration/drug effects
- T-Lymphocytes/cytology
- Tetradecanoylphorbol Acetate/pharmacology