Chen Hsin-Wei, Huang Hsing-I, Lee Yi-Ping, Chen Li-Li, Liu Hsiung-Kun, Cheng Mei-Lien, Tsai Jy-Ping, Tao Mi-Hua, Ting Chou-Chik
Immunology Group, National Health Research Institutes, Taipei, Taiwan.
Cancer Immunol Immunother. 2002 Aug;51(6):341-8. doi: 10.1007/s00262-002-0283-5. Epub 2002 Jun 14.
CD40-CD40 ligand (CD40L) interaction is an important costimulatory signal in the interaction between T cells and antigen-presenting cells (APC). In the present study, we determined whether the linkage of CD40L to the tumor-specific idiotype (Id) derived from a murine B-cell lymphoma, 38C13, could enhance its immunogenicity when presented by dendritic cells (DC). We showed that bone marrow-derived DC pulsed with Id-CD40L upregulated the expression of CD40, CD80, CD86, and major histocompatibility complex (MHC) class II molecules with the increased production of interleukin-12 (IL-12). Mice immunized with DC loaded with Id-CD40L showed high levels of anti-Id antibody response of both IgG2a and IgG1 isotypes. In addition, nylon wool-enriched T cells from these immunized mice showed a tumor-specific T-cell proliferative response upon stimulation with Id protein. Mice immunized with DC pulsed with Id alone failed to show any of these immune responses. Immunization with DC pulsed with Id-CD40L showed increased resistance to the challenge by 38C13 tumor, and tumor growth was significantly retarded. Together, these results show that linkage of CD40L to a self-tumor antigen enhances the anti-tumor immune response in DC-based treatment.
CD40与CD40配体（CD40L）的相互作用是T细胞与抗原呈递细胞（APC）相互作用中一种重要的共刺激信号。在本研究中，我们确定当树突状细胞（DC）呈递时，将CD40L与源自小鼠B细胞淋巴瘤38C13的肿瘤特异性独特型（Id）连接是否能增强其免疫原性。我们发现，用Id-CD40L脉冲处理的骨髓来源的DC上调了CD40、CD80、CD86和主要组织相容性复合体（MHC）II类分子的表达，同时白细胞介素-12（IL-12）的产生增加。用负载Id-CD40L的DC免疫的小鼠表现出高水平的IgG2a和IgG1同种型的抗Id抗体反应。此外，来自这些免疫小鼠的经尼龙毛富集的T细胞在用Id蛋白刺激后表现出肿瘤特异性T细胞增殖反应。用单独Id脉冲处理的DC免疫的小鼠未能表现出任何这些免疫反应。用Id-CD40L脉冲处理的DC免疫显示对38C13肿瘤攻击的抵抗力增加，并且肿瘤生长明显受到抑制。总之，这些结果表明在基于DC的治疗中，将CD40L与自身肿瘤抗原连接可增强抗肿瘤免疫反应。
