Isolation of a CD8alphaalpha+ CD4- tumour T-cell clone with cytotoxic activity from a CD4+ CD8- cutaneous T-cell lymphoma

Br J Dermatol. 2003 Jan;148(1):24-9. doi: 10.1046/j.1365-2133.2003.05015.x.

Abstract

Background: We have previously established tumour T-cell lines, both from the skin and from the blood of patients with a cutaneous T-cell lymphoma (CTCL). In one patient, the tumour cells and the derived cell lines had a CD3+ CD4+ CD8- phenotype and a trisomy of chromosome 7. They expressed three T-cell receptor (TCR) beta-chain transcripts, but only one was productively rearranged and expressed at the cell membrane.

Objectives: In the present study, we tried to isolate a fast-growing new tumour T-cell line from the same patient.

Patients/methods: We performed direct cell cloning of the skin tumour lymphocyte population, which led to the isolation of an interleukin-2-dependent highly proliferative T-cell subclone, named Cou-L3, with a CD3+ TCR-Vbeta13+ CD4- CD8alphaalpha+ phenotype.

Results: We demonstrated that Cou-L3 was identical to the original clonal tumour CD3+ Vbeta13+ CD4+ CD8- cells, as it expressed the same rearranged TCR-Vbeta13 chain. We further studied the functional activity of these CD8alphaalpha+ Vbeta13+ Cou-L3 cells. We found that these cells exhibited CD3-redirected cytotoxic activity.

Conclusions: An immunophenotypic shift, with a change from a CD4+ to a CD8+ phenotype, has been already reported in association with disease progression in CTCL. However, in these cases, there has been no demonstration that the phenotypic change involved the same T-cell clone. The present study is the first report of the phenotypic heterogeneity of the tumour clonal cell population in CTCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Lymphoma, T-Cell, Cutaneous / immunology
  • Lymphoma, T-Cell, Cutaneous / pathology*
  • Male
  • Mycosis Fungoides / pathology
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Receptors, Antigen, T-Cell / metabolism
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology*
  • T-Lymphocyte Subsets / immunology
  • Tumor Cells, Cultured*

Substances

  • CD3 Complex
  • Receptors, Antigen, T-Cell