Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors

J Immunol. 1994 Dec 1;153(11):5176-82.


There is considerable evidence to demonstrate that immune function is abnormal in tumor-bearing mice, perhaps accounting, at least in part, for progressive tumor growth. In an attempt to generate an antitumor response, we used retroviral vectors to express IL-2 cDNA in CMS5, a murine fibrosarcoma. Mice inoculated with unmodified tumor cells suffered progressive tumor growth, whereas tumors secreting IL-2 were rejected or grew slowly. Animals bearing unmodified but not IL-2-secreting tumors also were immunosuppressed. On the basis of these observations, we were interested in how IL-2 secretion by the tumor cells prevented the onset of hyporesponsiveness. To identify biochemical differences between T cells of mice with parental vs slowly growing IL-2-secreting tumors, we examined signal transduction after activation through the CD3/TCR complex. Protein tyrosine phosphorylation was altered and calcium flux was reduced in cells of mice with parental tumors compared with animals with slowly growing IL-2-secreting tumors. In addition, levels of protein for the tyrosine kinases p56lck and p59fyn, as well as the TCR-zeta-chain, were reduced. These differences in signal transduction were observed for T cells of mice with parental and IL-2-secreting tumors of the same size, demonstrating that differences in tumor size alone could not explain our findings. Thus, IL-2 secretion by tumors seems to be able to prevent immunosuppression by maintaining normal signal transduction in T cells, facilitating the generation of antitumor responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Fibrosarcoma / immunology*
  • Flow Cytometry
  • Immunoblotting
  • Interleukin-2 / metabolism*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fyn
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*


  • Interleukin-2
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-fyn
  • Calcium