title: Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells.
abstract: OBJECTIVE
  To determine whether the ability of primary myeloid dendritic cells (mDCs) to induce regulatory T cells (Treg) is affected by chronic simian immunodeficiency virus (SIV) infection.
  
  
  METHODS
  Modulation of dendritic cell activity with the aim of influencing Treg frequency may lead to new treatment options for HIV and strategies for vaccine development.
  
  
  METHODS
  Eleven chronically infected SIV(+) Rhesus macaques were compared with four uninfected animals. Immature and mature mDCs were isolated from mesenteric lymph nodes and spleen by cell sorting and cultured with purified autologous non-Treg (CD4(+)CD25(-) T cells). CD25 and FOXP3 up-regulation was used to assess Treg induction.
  
  
  RESULTS
  The frequency of splenic mDC and plasmacytoid dendritic cell was lower in infected animals than in uninfected animals; their frequency in the mesenteric lymph nodes was not significantly altered, but the percentage of mature mDCs was increased in the mesenteric lymph nodes of infected animals. Mature splenic or mesenteric mDCs from infected animals were significantly more efficient at inducing Treg than mDCs from uninfected animals. Mature mDCs from infected macaques induced more conversion than immature mDCs. Splenic mDCs were as efficient as mesenteric mDCs in this context and CD103 expression by mDCs did not appear to influence the level of conversion.
  
  
  CONCLUSIONS
  Tissue mDCs from SIV-infected animals exhibit an enhanced capability to induce Treg and may contribute to the accumulation of Treg in lymphoid tissues during progressive infection. The activation status of dendritic cell impacts this process but the capacity to induce Treg was not restricted to mucosal dendritic cells in infected animals.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Ohio, USA.
authors.forename: Pietro
authors.initials: P
authors.lastname: Presicce
authors.forename: Julia M
authors.initials: JM
authors.lastname: Shaw
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit
references.citation: Nat Med. 2006 Dec;12(12):1365-71
references.pmid: 17115046
references.citation: J Immunol. 2007 Jun 1;178(11):6958-67
references.pmid: 17513745
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):229-40
references.pmid: 21103670
references.citation: AIDS Res Hum Retroviruses. 2007 Mar;23(3):438-50
references.pmid: 17411377
references.citation: Immunology. 2009 Sep;128(1 Suppl):e366-75
references.pmid: 19016904
references.citation: Nat Immunol. 2000 Oct;1(4):311-6
references.pmid: 11017102
references.citation: Blood. 2007 Apr 1;109(7):2871-7
references.pmid: 17164341
references.citation: J Immunol. 2004 Mar 1;172(5):3189-95
references.pmid: 14978126
references.citation: Int Arch Allergy Immunol. 2002 Oct;129(2):113-8
references.pmid: 12403928
references.citation: J Virol. 2010 Apr;84(7):3259-69
references.pmid: 20071575
references.citation: J Immunol. 2005 Mar 15;174(6):3143-7
references.pmid: 15749840
references.citation: Blood. 2004 Nov 15;104(10):3249-56
references.pmid: 15271794
references.citation: J Acquir Immune Defic Syndr. 2008 May 1;48(1):1-12
references.pmid: 18300699
references.citation: AIDS Res Hum Retroviruses. 2011 Dec;27(12):1259-69
references.pmid: 21732792
references.citation: Mucosal Immunol. 2008 Nov;1 Suppl 1:S34-8
references.pmid: 19079226
references.citation: J Infect Dis. 2006 Feb 15;193(4):494-504
references.pmid: 16425128
references.citation: J Virol. 2008 Sep;82(17):8307-15
references.pmid: 18579608
references.citation: Immunol Rev. 2006 Aug;212:301-13
references.pmid: 16903922
references.citation: Immunity. 2009 May;30(5):626-35
references.pmid: 19464985
references.citation: Sci Transl Med. 2010 May 19;2(32):32ra36
references.pmid: 20484731
references.citation: J Infect Dis. 2003 Jan 1;187(1):26-37
references.pmid: 12508143
references.citation: Adv Immunol. 2010;108:111-65
references.pmid: 21056730
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3390-5
references.pmid: 17360656
references.citation: Nature. 1994 Nov 10;372(6502):190-3
references.pmid: 7969453
references.citation: Gut. 2010 May;59(5):595-604
references.pmid: 20427394
references.citation: J Infect Dis. 2009 Jun 15;199(12):1862-71
references.pmid: 19419334
references.citation: Blood. 2007 May 15;109(10):4272-9
references.pmid: 17289812
references.citation: Blood. 2006 Dec 1;108(12):3834-42
references.pmid: 16896154
references.citation: Clin Immunol. 2001 Nov;101(2):201-10
references.pmid: 11683579
references.citation: Curr Mol Med. 2009 Sep;9(7):836-50
references.pmid: 19860663
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: Infect Immun. 2007 Sep;75(9):4334-41
references.pmid: 17562772
references.citation: Blood. 2009 Jun 11;113(24):6112-9
references.pmid: 19366987
references.citation: Blood. 2006 Nov 1;108(9):3072-8
references.pmid: 16728694
references.citation: Blood. 2011 May 19;117(20):5372-80
references.pmid: 21436067
references.citation: J Infect Dis. 2006 Mar 1;193(5):703-12
references.pmid: 16453267
references.citation: Int Immunol. 2009 Mar;21(3):283-94
references.pmid: 19208751
references.citation: PLoS Pathog. 2009 May;5(5):e1000413
references.pmid: 19424421
references.citation: J Clin Invest. 2008 Oct;118(10):3431-9
references.pmid: 18776940
references.citation: Mucosal Immunol. 2009 May;2(3):254-64
references.pmid: 19262503
references.citation: Blood. 2006 Dec 1;108(12):3808-17
references.pmid: 16902147
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2588-92
references.pmid: 8637918
references.citation: AIDS. 2001 Sep 7;15(13):1657-63
references.pmid: 11546940
references.citation: Virology. 2007 Sep 1;365(2):356-68
references.pmid: 17490699
references.citation: Cell Biosci. 2011 May 24;1(1):20
references.pmid: 21711933
references.citation: J Infect Dis. 2007 Feb 15;195(4):551-61
references.pmid: 17230415
references.citation: Cell. 2008 May 30;133(5):775-87
references.pmid: 18510923
references.citation: PLoS One. 2010 May 24;5(5):e10788
references.pmid: 20520721
references.citation: Blood. 2001 Oct 15;98(8):2574-6
references.pmid: 11588058
references.citation: Eur J Immunol. 2008 Nov;38(11):3226-36
references.pmid: 18924219
references.citation: Blood. 2011 Sep 8;118(10):2763-73
references.pmid: 21693759
references.citation: Mucosal Immunol. 2009 Jul;2(4):340-50
references.pmid: 19387433
references.citation: AIDS. 1999 May 7;13(7):759-66
references.pmid: 10357374
references.citation: J Virol. 2004 May;78(10):5223-32
references.pmid: 15113904
references.citation: Blood. 2011 Jun 9;117(23):6184-92
references.pmid: 21505190
references.citation: J Virol. 2004 Mar;78(5):2454-9
references.pmid: 14963140
references.citation: PLoS One. 2010 Jun 14;5(6):e11110
references.pmid: 20559432
references.citation: Trends Immunol. 2002 Sep;23(9):445-9
references.pmid: 12200066
references.citation: Eur J Immunol. 2004 Mar;34(3):762-772
references.pmid: 14991606
references.citation: Trends Mol Med. 2009 Feb;15(2):41-9
references.pmid: 19162548
references.citation: Immunity. 2009 May;30(5):616-25
references.pmid: 19464984
references.citation: Science. 2011 Jan 21;331(6015):337-41
references.pmid: 21205640
references.citation: Nat Immunol. 2003 Jul;4(7):664-9
references.pmid: 12766766
references.citation: J Med Primatol. 2010 Aug;39(4):235-42
references.pmid: 20618589
references.citation: Blood. 2001 Aug 15;98(4):906-12
references.pmid: 11493432
references.citation: Eur J Immunol. 2007 Nov;37(11):3054-62
references.pmid: 17948274
references.citation: J Immunol. 2006 Nov 15;177(10):7103-13
references.pmid: 17082627
references.citation: Gut. 2009 Nov;58(11):1481-9
references.pmid: 19570762
references.citation: J Virol. 2007 Nov;81(21):11593-603
references.pmid: 17715231
references.citation: Blood. 2001 Nov 15;98(10):3016-21
references.pmid: 11698285
references.citation: J Immunol. 2002 May 1;168(9):4796-801
references.pmid: 11971031
references.citation: Transplantation. 2009 Nov 15;88(9):1057-64
references.pmid: 19898200
references.citation: J Exp Med. 2003 Dec 15;198(12):1875-86
references.pmid: 14676299
references.citation: J Med Primatol. 2010 Aug;39(4):243-51
references.pmid: 20618590
references.citation: J Exp Med. 2007 Aug 6;204(8):1757-64
references.pmid: 17620361
references.citation: Blood. 2006 Oct 15;108(8):2655-61
references.pmid: 16763205
references.citation: Immunity. 2008 Sep 19;29(3):362-71
references.pmid: 18799144
references.citation: Immunol Cell Biol. 2005 Oct;83(5):578-83
references.pmid: 16174110
references.citation: Blood. 2009 Jul 16;114(3):555-63
references.pmid: 19465693