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

Biochem Biophys Res Commun. 1989 Apr 14;160(1):181-8. doi: 10.1016/0006-291x(89)91638-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Receptors, Interleukin-2 / genetics
  • Regeneration* / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myb
  • Proto-Oncogene Proteins c-myc
  • Receptors, Interleukin-2
  • Concanavalin A
  • Calcimycin
  • Cyclophosphamide
  • Tetradecanoylphorbol Acetate