Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control

被引:168
作者
Mullins, DW
Sheasley, SL
Ream, RM
Bullock, TNJ
Fu, YX
Engelhard, VH
机构
[1] Univ Virginia, Carter Immunol Ctr, Charlottesville, VA 22908 USA
[2] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
[3] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
关键词
active immunotherapy; regional immunity; vaccination; T cell memory; T cell homing;
D O I
10.1084/jem.20021348
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1023 / 1034
页数:12
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