Functional characterization of an IL-7-dependent CD4(+)CD8alphaalpha(+) Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma.
CDR3 of the functional rearranged T-cell receptor variable beta region (TCR-Vbeta) 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(+)Vbeta22(+)CD4(+)CD8alphaalpha(+)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 beta-myristate 13 alpha-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-beta1 (TGF-beta1). This high production of TGF-beta1 may inhibit antitumor specific responses in CTCL.
Poszepczynska
E
E
Institut National de la Santé et de la Recherche Médicale (INSERM) Créteil, France.
Bagot
M
M
Echchakir
H
H
Martinvalet
D
D
Ramez
M
M
Charue
D
D
Boumsell
L
L
Bensussan
A
A
D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology*; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D016827:CD8 Antigens; D015851:Interleukin-7