Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma

Leukemia. 2004 Jan;18(1):126-32. doi: 10.1038/sj.leu.2403176.


Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNgamma in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.

Publication types

  • Comparative Study

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Chromium / metabolism
  • Gene Products, tax / immunology*
  • HLA-A2 Antigen / analysis
  • HTLV-I Antibodies / biosynthesis
  • Human T-lymphotropic virus 1 / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / classification
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Leukocytes, Mononuclear / immunology
  • Peptide Fragments / pharmacology
  • Receptors, Antigen, T-Cell / analysis
  • T-Lymphocytes, Cytotoxic / immunology*


  • Gene Products, tax
  • HLA-A2 Antigen
  • HTLV-I Antibodies
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Chromium
  • Interferon-gamma