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Isolation of Tumor-Specific Cytotoxic CD4+ and
CD4+CD8dim+ T-Cell Clones Infiltrating a
Cutaneous T-Cell Lymphoma
Martine Bagot,
Hamid Echchakir,
Fathia Mami-Chouaib,
Marie-Hélène Delfau-Larue,
Dominique Charue,
Alain Bernheim,
Salem Chouaib,
Laurence Boumsell, and
Armand Bensussan
From INSERM U448, Paris XII University, Paris; the Department of
Dermatology, Hôpital Henri Mondor, Créteil; INSERM U487 and
CNRS-URA 1967, Institut Gustave Roussy, Villejuif,
France.
We have isolated several T-cell clones from lymphocytes infiltrating
a human major histocompatibility class (MHC) II negative cutaneous
T-cell lymphoma (CTCL). We describe here two of these clones, TC5 and
TC7, with, respectively, a CD4+CD8dim+ and
CD4+CD8 phenotype. Both clones mediated a
specific MHC class I-restricted cytotoxic activity toward the fresh
autologous tumor cells, and autologous tumor cell lines previously
established with interleukin-2 (IL-2) and IL-7 from the skin and from
the blood. Analysis of the T-cell receptor (TCR) V gene expression
showed that the tumor cells, which were shown to have a trisomy 7 by
fluorescent in situ hybridization, expressed V7/J2.3,
V13/J2.5, and V22/J2.5 rearrangements. Phenotypic analysis
using specific anti-V monoclonal antibodies indicated that only
V13 could be detected on the cell membrane of the tumor cells.
Analysis of the TCR V gene expression of the clones showed that TC5
and TC7 expressed a unique TCR-V transcript, corresponding,
respectively, to V5/J2.3 and V17/J2.7 gene segments. To
determine whether these reactive T lymphocytes were present in vivo, we
used specific primers corresponding to TC5- and TC7-V TCR
transcripts. The results showed that both cytotoxic T-cell clones were
present at the lesional skin site and amplified in vitro. TC7 was found
in the patient peripheral blood invaded by tumoral cells, whereas TC5
was not, indicating that the repertoire of the reactional lymphocytes
differs in the blood and at the tumor site. These results show for the
first time the presence of reactive T lymphocytes with CD4 or
double-positive phenotype infiltrating a CTCL. These findings raise the
question of the role of these antitumoral effector T cells in the tumor growth.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4331-4341
© 1998 by The American Society of Hematology.
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