Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells.
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.
Kusmartsev
Sergei
S
H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA.
Nagaraj
Srinivas
S
Gabrilovich
Dmitry I
DI
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm