Berger Carole L, Hanlon Douglas, Kanada Daniel, Dhodapkar Madhav, Lombillo Vivian, Wang Nianci, Christensen Inger, Howe Gregory, Crouch Jill, El-Fishawy Paul, Edelson Richard
Yale University, School of Medicine, Department of Dermatology and Laboratory Medicine, New Haven, CT 06510, USA.
Blood. 2002 Apr 15;99(8):2929-39.
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.
在皮肤T细胞淋巴瘤（CTCL）的初始阶段，增殖的CTCL细胞集中在表皮中，与未成熟的树突状细胞（DC）即朗格汉斯细胞密切相关。由于已证明CTCL细胞的长期体外培养很困难，因此推测其与表皮主要抗原呈递细胞（APC）的体内关联在直接刺激克隆性T细胞增殖中起作用。我们报告，当与未成熟DC共培养时，CTCL细胞可在培养物中可重复生长3个月。CTCL细胞保留了初始恶性克隆的表型和基因型，而APC是未成熟和成熟DC的混合物。CTCL细胞和DC的存活取决于直接的膜接触。与T细胞受体（TCR）结合或干扰CD40与其在CTCL细胞上的配体相互作用的抗体可抑制生长。添加抗CD3或克隆型TCR抗体可导致CTCL细胞迅速凋亡，随后被吞噬活跃的未成熟DC吞噬并随后使DC成熟。长时间研究CTCL细胞和未成熟DC的机会将有助于肿瘤细胞生物学的研究，并将允许研究有趣的假说，即CTCL细胞的生长是通过TCR识别II类呈递的自身肽来驱动的。此外，CTCL细胞的培养将允许在临床干预之前在体外评估疗法，从而提高安全性和疗效。
