Restoration of abated T cell stimulation activity of mature dendritic cells.
Freshly isolated and cultured mature dendritic cells (DC) rapidly lose their high capacity to activate T cells. This diminished T cell activation activity is due, in part, to dramatically reduced expression of the costimulation ligands B7-1 (CD80) and B7-2 (CD86). Here we show that cultivation of mature DC with the lymphokines TNFalpha, GM-CSF, or TNFalpha plus GM-CSF, fully restored and enhanced their T-cell stimulation activity by two to threefold, four to fivefold, or six to sevenfold, respectively. The restored T-cell stimulation activity was directly correlated with induced and increased levels of CD80 (16-fold) and CD86 (10-fold) expression by the lymphokine-cultured DC. These results should facilitate many current DC-vaccination efforts towards generating more potent T cell responses.
Holowachuk
E W
EW
Research Institute, Mary Imogene Bassett Hospital, One Atwell Road, Cooperstown, NY 13326, USA. geneh@telenet.net
Ruhoff
M S
MS
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008198:Lymph Nodes; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor