Evidence for an interleukin-independent pathway for human lymphocyte activation

Proc Natl Acad Sci U S A. 1983 Jun;80(11):3444-7. doi: 10.1073/pnas.80.11.3444.


Though lectin mitogen stimulation of T-cell proliferation is an interleukin 1- (IL 1), interleukin 2- (IL 2) dependent process, the calcium ionophore A23187 may be able to initiate T-lymphocyte proliferation by an additional pathway. That the action of A23187 is IL 1 independent was demonstrated by its ability to stimulate monocyte-depleted cells without the addition of exogenous IL 1. The IL 2 independence of A23187 was indicated by (i) the inability of exogenous IL 2 to augment A23187-induced proliferation and (ii) the inability of the monoclonal antibody anti-Tac (with specificity for the human IL 2 receptor) to inhibit proliferation mediated by A23187. By contrast, in cultures stimulated with the lectin mitogen phytohemagglutinin, additional IL 2 considerably increased proliferation, whereas anti-Tac routinely caused 60-90% inhibition. Although the ionophore caused some IL 2 production and resulted in IL 2 receptor expression, quantitative studies showed that our results could not be explained by excessive amounts of endogenous IL 2 interfering with the blocking action of the antibody. Therefore, these data suggest that the action of A23187 as a human lymphocyte mitogen may be the result of at least two pathways--one dependent on the interleukin-cell interactions and the other independent of these mediators.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Calcimycin / pharmacology*
  • Cells, Cultured
  • DNA Replication / drug effects
  • Fluorescent Antibody Technique
  • Humans
  • Interleukin-1 / physiology
  • Interleukin-2 / physiology
  • Lymphocyte Activation* / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Anti-Bacterial Agents
  • Interleukin-1
  • Interleukin-2
  • Calcimycin