The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells.
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.
Berger
Carole L
CL
Yale University, School of Medicine, Department of Dermatology and Laboratory Medicine, New Haven, CT 06510, USA. carole.berger@yale.edu
Hanlon
Douglas
D
Kanada
Daniel
D
Dhodapkar
Madhav
M
Lombillo
Vivian
V
Wang
Nianci
N
Christensen
Inger
I
Howe
Gregory
G
Crouch
Jill
J
El-Fishawy
Paul
P
Edelson
Richard
R
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D017252:CD3 Complex / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000473:pathology*; D010587:Phagocytosis
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D016207:Cytokines; D006680:HLA Antigens