Berger Carole L, Tigelaar Robert, Cohen Justine, Mariwalla Kavita, Trinh Jennifer, Wang Nianci, Edelson Richard L
Department of Dermatology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, USA.
Blood. 2005 Feb 15;105(4):1640-7. doi: 10.1182/blood-2004-06-2181. Epub 2004 Oct 28.
Studies in an in vitro model of cutaneous T-cell lymphoma (CTCL) demonstrated that CTCL cell proliferation is stimulated by direct contact with autologous, immature dendritic cells (DCs), suggesting that CD4(+) CTCL cell division is driven by antigens presented by DC major histocompatibility complex (MHC) class 2. We now report that the T-cell receptor (TCR) of the CD4(+) CTCL cells is triggered after interaction with DCs loaded with apoptotic CTCL cells, as shown by reduced membrane expression of CD3 and the TCR, up-regulation of cytotoxic T lymphocyte antigen-4 (CTLA-4), and calcium mobilization. CTCL cells adopt a T-regulatory (Treg) phenotype expressing CD25/CTLA-4 and FoxP3 and secreting interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Treg CTCL cells suppress normal T-cell antigen-driven secretion of IL-2 and interferon-gamma (IFN-gamma). Blocking DC MHC class 2 expression or transport inhibited CTCL cell adoption of a Treg phenotype. Allogeneic CTCL cells or normal CD4 T cells served as sources of apoptotic material for CTCL cell conversion to a Treg phenotype. Conversion of CTCL cells to Treg cells may explain the anergic, immunosuppressive nature of the malignancy.
在皮肤T细胞淋巴瘤（CTCL）的体外模型研究表明，CTCL细胞增殖是由与自体未成熟树突状细胞（DCs）直接接触所刺激，这表明CD4(+) CTCL细胞分裂是由DC主要组织相容性复合体（MHC）II类所呈递的抗原驱动。我们现在报告，在与负载凋亡CTCL细胞的DC相互作用后，CD4(+) CTCL细胞的T细胞受体（TCR）被触发，表现为CD3和TCR的膜表达降低、细胞毒性T淋巴细胞抗原-4（CTLA-4）上调以及钙动员。CTCL细胞呈现表达CD25/CTLA-4和FoxP3并分泌白细胞介素-10（IL-10）和转化生长因子-β（TGF-β）的调节性T细胞（Treg）表型。Treg CTCL细胞抑制正常T细胞抗原驱动的IL-2和干扰素-γ（IFN-γ）分泌。阻断DC MHC II类表达或转运可抑制CTCL细胞向Treg表型的转变。同种异体CTCL细胞或正常CD4 T细胞用作CTCL细胞转化为Treg表型的凋亡物质来源。CTCL细胞向Treg细胞的转化可能解释了该恶性肿瘤的无反应性、免疫抑制性质。
