First Author | Ribas A | Year | 2004 |
Journal | J Immunol | Volume | 172 |
Issue | 8 | Pages | 4762-9 |
PubMed ID | 15067052 | Mgi Jnum | J:89152 |
Mgi Id | MGI:3038568 | Doi | 10.4049/jimmunol.172.8.4762 |
Citation | Ribas A, et al. (2004) Enhanced tumor responses to dendritic cells in the absence of CD8-positive cells. J Immunol 172(8):4762-9 |
abstractText | Wild-type mice immunized with MART-1 melanoma Ag-engineered dendritic cells (DC) generate strong Ag-specific immunity that has an absolute requirement for both CD8(+) and CD4(+) T cells. DC administration to CD8 alpha knockout mice displayed unexpectedly enhanced levels of protection to tumor challenge despite this deficiency in CD8(+) T cells and the inability to mount MHC class I-restricted immune responses. This model has the following features: 1) antitumor protection is Ag independent; 2) had an absolute requirement for CD4(+) and NK1.1(+) cells; 3) CD4(+) splenocytes are responsible for cytokine production; 4) lytic cells in microcytotoxicity assays express NK, but lack T cell markers (NK1.1(+) alpha beta TCR(-) CD3(-)); and 5) the lytic phenotype can be transferred to naive CD8 alpha knockout mice by NK1.1(+) splenocytes. Elucidation of the signaling events that activate these effective cytotoxic cells and the putative suppressive mechanisms in a wild-type environment may provide means to enhance the clinical activity of DC-based approaches. |