Production and regulation of interleukin-2 in human lymphoblastic leukemias studied with T-cell monoclonal antibodies

Blood. 1983 Apr;61(4):781-9.

Abstract

Human leukemias are illnesses of hemopoietic stem cells that go through processes of self-replication and partial differentiation under the control of as yet largely unknown growth and differentiation factors. IL-2 is a powerful factor controlling proliferation of normal T cells. We report that acute lymphoblastic leukemias of T and non-B, non-T phenotypes produce a growth factor after mitogen stimulation. This factor is able to support the proliferation of human and murine IL-2-dependent cytotoxic cells, has a mol wt of 26,000 daltons by gel filtration, an isoelectric point of 6.6, and its biologic activity is inhibited by an anti IL-2 monoclonal antibody. This factor is, therefore, by all parameters studied very similar to IL-2 produced by normal lymphocytes. A recently developed monoclonal antibody, Pan T2, binds to normal T cells, renders T cells responsive to IL-2, and induces the release of IL-2, which in turn provides the second signal for T-cell proliferation. Mononuclear cells from acute lymphoblastic leukemia do not respond to the addition of this monoclonal antibody unless cocultured with irradiated Daudi cells. Since normal T cells do not require Daudi to produce IL-2 and since Daudi cells do not produce IL-2 under any conditions, we conclude that the cell responsible for IL-2 production in acute lymphatic leukemia is a leukemic T cell with an altered mechanism of IL-2 production at the level of the Pan T2 binding site.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • B-Lymphocytes / immunology
  • Binding Sites, Antibody
  • Cell Line
  • Humans
  • Interleukin-2 / biosynthesis*
  • Leukemia, Lymphoid / immunology*
  • Leukemia, Lymphoid / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • Interleukin-2
  • Receptors, Antigen, T-Cell