IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients

Int J Cancer. 1986 Aug 15;38(2):265-74. doi: 10.1002/ijc.2910380218.

Abstract

Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL-2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A-stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation.

MeSH terms

  • Adult
  • Antigens, Surface / analysis
  • Antigens, Viral / analysis
  • Cell Division / drug effects
  • Cell Line
  • Deltaretrovirus Infections / etiology*
  • ErbB Receptors
  • Genes, Viral
  • HIV Antigens
  • Humans
  • Interleukin-2* / analysis
  • Male
  • Phenotype
  • Receptors, Cell Surface / analysis
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / genetics
  • Receptors, Interleukin-2
  • T-Lymphocytes / pathology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, Surface
  • Antigens, Viral
  • HIV Antigens
  • Interleukin-2
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • ErbB Receptors
  • Tetradecanoylphorbol Acetate