期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 7, 页码 4583-4592出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.7.4583
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资金
- NCI NIH HHS [R01 CA084488-04, R01 CA084488, CA84488] Funding Source: Medline
T cell tolerance is a critical element of tumor escape. However, the mechanism of tumor-associated T cell tolerance remains unresolved. Using an experimental system utilizing the adoptive transfer of transgenic T cells into naive recipients, we found that the population of Gr-1(+) immature myeloid cells (ImC) from tumor-bearing mice was able to induce CD8(+) T cell tolerance. These ImC accumulate in large numbers in spleens, lymph nodes, and tumor tissues of tumor-bearing mice and are comprised of precursors of myeloid cells. Neither ImC from control mice nor progeny of tumor-derived ImC, including tumor-derived CD11c(+) dendritic cells, were able to render T cells nonresponsive. ImC are able to take up soluble protein in vivo, process it, and present antigenic epitopes on their surface and induce Ag-specific T cell anergy. Thus, this is a first demonstration that in tumor-bearing mice CD8(+) T cell tolerance is induced primarily by ImC that may have direct implications for cancer immunotherapy.
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