Mullins David W, Sheasley Stacey L, Ream Rebecca M, Bullock Timothy N J, Fu Yang-Xin, Engelhard Victor H
Carter Immunology Center, University of Virginia, Box 801386, Charlottesville, VA 22908, USA.
J Exp Med. 2003 Oct 6;198(7):1023-34. doi: 10.1084/jem.20021348.
We have established that the route of immunization with peptide-pulsed, activated DC leads to memory CD8+ T cells with distinct distributions in lymphoid tissues, which determines the ability to control tumors growing in different body sites. Both intravenous (i.v.) and subcutaneous (s.c.) immunization induced memory T cells in spleen and control of metastatic-like lung tumors. s.c. immunization also induced memory T cells in lymph nodes (LNs), imparting protection against subcutaneously growing tumors. In contrast, i.v. immunization-induced memory was restricted to spleen and failed to impart protective immunity against subcutaneously growing tumors. Memory cell distribution and tumor control were both linked to injection route-dependent localization of DCs in lymphoid compartments. Using peripheral LN-ablated mice, these LNs were shown to be essential for control of subcutaneously growing tumors but not lung metastases; in contrast, using immunized asplenic mice, we found that the spleen is necessary and sufficient for control of lung tumors, but unnecessary for control of subcutaneously growing tumors. These data demonstrate the existence of a previously undescribed population of splenic-resident memory CD8 T cells that are essential for the control of lung metastases. Thus, regional immunity based on memory T cell residence patterns is an important factor in DC-based tumor immunotherapy.
我们已经证实，用肽脉冲激活的树突状细胞（DC）进行免疫接种的途径会导致记忆性CD8+T细胞在淋巴组织中具有不同的分布，这决定了控制在不同身体部位生长的肿瘤的能力。静脉内（i.v.）和皮下（s.c.）免疫接种均可诱导脾脏中的记忆性T细胞并控制转移性肺癌样肿瘤。皮下免疫接种还可诱导淋巴结（LN）中的记忆性T细胞，从而提供针对皮下生长肿瘤的保护作用。相比之下，静脉内免疫接种诱导的记忆仅限于脾脏，并且未能提供针对皮下生长肿瘤的保护性免疫。记忆细胞分布和肿瘤控制均与DC在淋巴区室中的注射途径依赖性定位有关。使用外周淋巴结切除的小鼠，这些淋巴结被证明对于控制皮下生长的肿瘤至关重要，但对肺转移则不然；相反，使用免疫的无脾小鼠，我们发现脾脏对于控制肺肿瘤是必要且充分的，但对于控制皮下生长的肿瘤则不必要。这些数据证明存在以前未描述的脾脏驻留记忆CD8 T细胞群体，它们对于控制肺转移至关重要。因此，基于记忆T细胞驻留模式的区域免疫是基于DC的肿瘤免疫治疗中的一个重要因素。
