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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1056-1063
Functional characterization of an IL-7-dependent
CD4+CD8 + Th3-type malignant cell line
derived from a patient with a cutaneous T-cell lymphoma
Eva Poszepczynska,
Martine Bagot,
Hamid Echchakir,
Denis Martinvalet,
Mohamed Ramez,
Dominique Charue,
Laurence Boumsell, and
Armand Bensussan
From Institut National de la Santé et de la
Recherche Médicale (INSERM) 448, IM3, Paris XII, Hôpital
Henri Mondor, Créteil, France.
CDR3 of the functional rearranged T-cell receptor
variable  region (TCR-V) transcript was sequenced in
order to demonstrate for the first time the identity between a
long-term cultured T-cell line derived from a cutaneous T-cell lymphoma
(CTCL) patient and the malignant T-cell clone present in the blood. The
patient's peripheral blood lymphocyte-derived cultured T-cell line had
a CD3+V22+CD4+CD8 +CD25
phenotype. It was named Pno and had been cultured for more than 1 year.
Both fresh and long-term-cultured tumor cells proliferated highly in
response to interleukin-7 (IL-7), and exogeneous IL-7 prevented Pno
lymphocytes from apoptosis and maintained high levels of
Bcl-2 expression. This unique malignant cloned lymphocyte
line was further used to carry out functional studies. The results indicated that the CD3/TCR structures expressed by the Pno lymphocytes were functional because an immobilized anti-CD3 monoclonal antibody (mAb) or the combination of a soluble anti-CD3 mAb with submitogenic doses of phorbol 12 -myristate 13 -acetate induced a
proliferative response. Further, the CD2 and CD28 coreceptors were
functional because they were able to induce a strong proliferative
response upon their specific stimulation. Finally, the Pno T cell line had a Th3-type cytokine profile because it produced high amounts of the
immunosuppressor cytokine tumor growth factor-1 (TGF-1). This
high production of TGF-1 may inhibit antitumor specific responses in CTCL.
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