Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia

Cancer Res. 1985 Sep;45(9 Suppl):4559s-4562s.

Abstract

Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Cell Line
  • Deltaretrovirus* / genetics
  • Genes, Viral
  • Humans
  • Leukemia / blood
  • Leukemia / microbiology*
  • Leukemia / therapy
  • Lymphocyte Activation
  • Male
  • Receptors, Immunologic / analysis
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / isolation & purification
  • Receptors, Interleukin-2
  • Retroviridae Infections / blood
  • Retroviridae Infections / microbiology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / microbiology
  • Transcription Factors
  • Transcription, Genetic
  • Viral Proteins / genetics
  • Viral Proteins / physiology

Substances

  • Antibodies, Monoclonal
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Transcription Factors
  • Viral Proteins