Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice.
The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.
May
Kenneth F
KF
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH, USA.
Lute
Kenneth
K
Kocak
Ergun
E
Abdessalam
Shahab
S
Yin
Lijie
L
Li
Ou
O
Guan
Zhen
Z
Philips
Gary
G
Zheng
Pan
P
Liu
Yang
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D016026:Bone Marrow Transplantation; D017637:Clonal Deletion; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D007121:Immunocompetence; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018448:Models, Immunological; D010954:Plasmacytoma / Q000276:immunology* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C076546:tumor rejection antigen P815A, mouse