PMID- 15128934 OWN - NLM STAT- MEDLINE DCOM- 20040706 LR - 20220318 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 101 IP - 20 DP - 2004 May 18 TI - HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation. PG - 7669-74 AB - Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced. FAU - Granelli-Piperno, Angela AU - Granelli-Piperno A AD - Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. piperno@rockefeller.edu FAU - Golebiowska, Angelika AU - Golebiowska A FAU - Trumpfheller, Christine AU - Trumpfheller C FAU - Siegal, Frederick P AU - Siegal FP FAU - Steinman, Ralph M AU - Steinman RM LA - eng GR - R01 AI040045/AI/NIAID NIH HHS/United States GR - M01 RR000102/RR/NCRR NIH HHS/United States GR - P30 AI042848/AI/NIAID NIH HHS/United States GR - 5 P30 AI 42848-04/AI/NIAID NIH HHS/United States GR - R01 AI40045/AI/NIAID NIH HHS/United States GR - M0-1 RR00102/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040505 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 130068-27-8 (Interleukin-10) SB - IM MH - Coculture Techniques MH - Dendritic Cells/physiology/*virology MH - HIV-1/*metabolism MH - HeLa Cells MH - Humans MH - Interleukin-10/*biosynthesis MH - T-Lymphocytes/*physiology PMC - PMC419664 EDAT- 2004/05/07 05:00 MHDA- 2004/07/09 05:00 PMCR- 2004/11/18 CRDT- 2004/05/07 05:00 PHST- 2004/05/07 05:00 [pubmed] PHST- 2004/07/09 05:00 [medline] PHST- 2004/05/07 05:00 [entrez] PHST- 2004/11/18 00:00 [pmc-release] AID - 0402431101 [pii] AID - 1017669 [pii] AID - 10.1073/pnas.0402431101 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2004 May 18;101(20):7669-74. doi: 10.1073/pnas.0402431101. Epub 2004 May 5.