IngentaConnect Isolation of a CD8alphaalpha+ CD4- tumour T-cell clone with cytot...

Authors: Nikolova M.¹; Echchakir H.¹; Wechsler J.²; Boumsell L.¹; Bensussan A.¹; Bagot M.¹

Source: British Journal of Dermatology, Volume 148, Number 1, January 2003 , pp. 24-29(6)

Abstract:

Summary 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) bgr

-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-V bgr

13+ CD4– CD8 agr

+ phenotype. Results

We demonstrated that Cou-L3 was identical to the original clonal tumour CD3+ V bgr

13+ CD4+ CD8– cells, as it expressed the same rearranged TCR-V bgr

13 chain. We further studied the functional activity of these CD8 agr

+ V

13+ 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.

Keywords: CD8 agr agr lymphocyte; cutaneous T-cell lymphoma; cytotoxic T lymphocyte; lymphocyte differentiation; T-cell receptor

Document Type: Research article

DOI: 10.1046/j.1365-2133.2003.05015.x

Affiliations: 1: INSERM U448, Department of Dermatology, Hôpital Henri Mondor, 94010 Cre´teil, France 2: Department of Pathology, Hôpital Henri Mondor, 94010 Cre´teil, France

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