PMID- 10411546 OWN - NLM STAT- MEDLINE DCOM- 19990812 LR - 20240508 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 104 IP - 2 DP - 1999 Jul TI - Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. PG - 173-80 AB - Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity. FAU - Dhodapkar, M V AU - Dhodapkar MV AD - Laboratory of Immunology and Cellular Physiology, General Clinical Research Center, and Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10021, USA. dhodapm@rockvax.rockefeller.edu FAU - Steinman, R M AU - Steinman RM FAU - Sapp, M AU - Sapp M FAU - Desai, H AU - Desai H FAU - Fossella, C AU - Fossella C FAU - Krasovsky, J AU - Krasovsky J FAU - Donahoe, S M AU - Donahoe SM FAU - Dunbar, P R AU - Dunbar PR FAU - Cerundolo, V AU - Cerundolo V FAU - Nixon, D F AU - Nixon DF FAU - Bhardwaj, N AU - Bhardwaj N LA - eng GR - R01 AI044628/AI/NIAID NIH HHS/United States GR - R01 AI040874/AI/NIAID NIH HHS/United States GR - M01 RR000102/RR/NCRR NIH HHS/United States GR - R01 AI044595/AI/NIAID NIH HHS/United States GR - AI-40874/AI/NIAID NIH HHS/United States GR - AI-44628/AI/NIAID NIH HHS/United States GR - AI-39516/AI/NIAID NIH HHS/United States GR - R37 AI044628/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (HLA-A Antigens) SB - IM MH - Adolescent MH - Adult MH - Aged MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Dendritic Cells/*immunology MH - Female MH - HLA-A Antigens/analysis MH - Humans MH - Immunization MH - Male MH - Middle Aged MH - T-Lymphocytes/*immunology PMC - PMC408478 EDAT- 1999/07/20 00:00 MHDA- 1999/07/20 00:01 PMCR- 1999/07/15 CRDT- 1999/07/20 00:00 PHST- 1999/07/20 00:00 [pubmed] PHST- 1999/07/20 00:01 [medline] PHST- 1999/07/20 00:00 [entrez] PHST- 1999/07/15 00:00 [pmc-release] AID - 06909 [pii] AID - 10.1172/JCI6909 [doi] PST - ppublish SO - J Clin Invest. 1999 Jul;104(2):173-80. doi: 10.1172/JCI6909.