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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2929-2939
IMMUNOBIOLOGY
The growth of cutaneous T-cell lymphoma is stimulated by
immature dendritic cells
Carole L. Berger,
Douglas Hanlon,
Daniel Kanada,
Madhav Dhodapkar,
Vivian Lombillo,
Nianci Wang,
Inger Christensen,
Gregory Howe,
Jill Crouch,
Paul El-Fishawy, and
Richard Edelson
From Yale University, School of Medicine, Department of
Dermatology and Laboratory Medicine, New Haven, CT; Rockefeller
University, Laboratory of Tumor Immunology and Immunotherapy, and the
Memorial Sloan-Kettering Cancer Center, New York, NY.
In the initial stage of cutaneous T-cell lymphoma (CTCL),
proliferating CTCL cells are concentrated in the epidermis in close association with an immature dendritic cell (DC), the Langerhans cell.
Because long-term in vitro culture of CTCL cells has proven difficult,
the in vivo association with the major antigen-presenting cell (APC) of
the epidermis has been postulated to play a role in directly
stimulating the clonal T-cell proliferation. We report that CTCL cells
can be reproducibly grown in culture for 3 months when cocultured with
immature DCs. CTCL cells retain the phenotype and genotype of the
initial malignant clone, whereas the APCs are a mixture of immature and
mature DCs. CTCL cell and DC survival was dependent on direct membrane
contact. Growth was inhibited by antibodies that bound to the T-cell
receptor (TCR) or interfered with the interaction of CD40 with its
ligand on the CTCL cell. Addition of antibody to CD3 or the clonotypic
TCR caused rapid CTCL cell apoptosis followed by engulfment by avidly
phagocytic immature DCs and subsequent DC maturation. The opportunity
to study CTCL cells and immature DCs for prolonged periods will
facilitate studies of tumor cell biology and will allow investigation
of the intriguing hypothesis that CTCL cell growth is driven through TCR recognition of class II-presented self-peptides. In addition, the
culture of CTCL cells will permit evaluation of therapies in vitro
before clinical intervention, thereby improving safety and efficacy.
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