Mechanism of T cell proliferation in vivo: analysis of IL-2 receptor expression and activation of c-myc and c-myb oncogenes during lymphatic regeneration

M Sihvola, L Sistonen, K Alitalo, M Hurme

Research output: Contribution to journalArticleScientificpeer-review


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 languageEnglish
Pages (from-to)181-8
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 14 Apr 1989
MoE publication typeA1 Journal article-refereed


  • 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


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