title: Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow-derived dendritic cells.
abstract: Dendritic cells (DCs) are the most important antigen-presenting cells of the immune system and have a crucial role in T-lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4(+) CD25(+) Foxp3(+) T-cell population after co-culture of lymph node cells from BALB/c mice with syngeneic bone marrow-derived DCs. Our results showed an increase in CD4(+) CD25(+) Foxp3(+) T cells after co-culture which occurred regardless of the activation state of DCs and the presence of allogeneic apoptotic cells; however, it was greater when DCs were immature and were pulsed with the alloantigen. Interestingly, syngeneic apoptotic thymocytes were not as efficient as allogeneic apoptotic cells in expanding the CD4(+) CD25(+) Foxp3(+) T-cell population. In all experimental settings, DCs produced high amounts of transforming growth factor (TGF)-beta. The presence of allogeneic apoptotic cells induced interleukin (IL)-2 production in immature and mature DC cultures. This cytokine was also detected in the supernatants under all experimental conditions and enhanced when immature DCs were pulsed with the alloantigen. CD4(+) CD25(+) Foxp3(+) T-cell expansion during co-culture of lymph node cells with DCs strongly suggested that the presence of alloantigen enhanced the number of regulatory T cells (Tregs) in vitro. Our data also suggest a role for both TGF-beta and IL-2 in the augmentation of the CD4(+) CD25(+) Foxp3(+) population.
authors.affiliation: Laboratory of Clinical Immunology, Department of Immunology, Instituto de Ciências Biomédicas, University of São Paulo, São Paulo, Brazil.
authors.forename: Ivo
authors.initials: I
authors.lastname: Marguti
authors.forename: Guilherme Lopes
authors.initials: GL
authors.lastname: Yamamoto
authors.forename: Thaís Boccia
authors.initials: TB
authors.lastname: da Costa
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.forename: Luciana Vieira
authors.initials: LV
authors.lastname: de Moraes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2
references.citation: Blood. 1999 Mar 1;93(5):1634-42
references.pmid: 10029592
references.citation: Nat Immunol. 2005 Dec;6(12):1219-27
references.pmid: 16244650
references.citation: Annu Rev Immunol. 2002;20:621-67
references.pmid: 11861614
references.citation: Immunol Rev. 2006 Aug;212:8-27
references.pmid: 16903903
references.citation: J Immunol. 2002 Feb 15;168(4):1627-35
references.pmid: 11823490
references.citation: J Exp Med. 2002 Oct 21;196(8):1091-7
references.pmid: 12391020
references.citation: J Immunol. 1997 Nov 15;159(10):4772-80
references.pmid: 9366401
references.citation: Clin Exp Immunol. 2003 Jul;133(1):50-8
references.pmid: 12823278
references.citation: Semin Immunol. 2006 Apr;18(2):93-102
references.pmid: 16469503
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8750-5
references.pmid: 11447263
references.citation: Am J Transplant. 2006 Jun;6(6):1297-311
references.pmid: 16686754
references.citation: Immunity. 2003 May;18(5):605-17
references.pmid: 12753738
references.citation: J Exp Med. 1998 Dec 7;188(11):2163-73
references.pmid: 9841929
references.citation: Blood. 2001 Jul 1;98(1):224-30
references.pmid: 11418484
references.citation: J Exp Med. 2002 Dec 16;196(12):1553-61
references.pmid: 12486098
references.citation: J Exp Med. 2005 Apr 4;201(7):1061-7
references.pmid: 15809351
references.citation: Blood. 2006 Oct 15;108(8):2655-61
references.pmid: 16763205
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2821-6
references.pmid: 17307871
references.citation: J Clin Invest. 2005 Jul;115(7):1923-33
references.pmid: 15937545
references.citation: Cell Death Differ. 2006 Jan;13(1):41-52
references.pmid: 15962005
references.citation: Science. 2003 Feb 14;299(5609):1057-61
references.pmid: 12522256
references.citation: Nat Immunol. 2006 Jun;7(6):652-62
references.pmid: 16633346
references.citation: J Immunol. 1999 May 1;162(9):5317-26
references.pmid: 10228007
references.citation: J Exp Med. 1992 Dec 1;176(6):1693-702
references.pmid: 1460426
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2758-63
references.pmid: 16473944
references.citation: Science. 1995 Jun 9;268(5216):1472-6
references.pmid: 7770771
references.citation: J Immunol. 2007 Aug 15;179(4):2170-9
references.pmid: 17675476
references.citation: J Exp Med. 2003 Jul 21;198(2):235-47
references.pmid: 12874257
references.citation: J Exp Med. 2000 Nov 6;192(9):1213-22
references.pmid: 11067871
references.citation: J Exp Med. 2000 Feb 7;191(3):411-6
references.pmid: 10662786
references.citation: J Immunol. 2003 Feb 1;170(3):1304-12
references.pmid: 12538690
references.citation: Blood. 2007 Dec 15;110(13):4293-302
references.pmid: 17699744
references.citation: Blood. 2003 Jan 15;101(2):611-20
references.pmid: 12393562
references.citation: J Immunol. 2004 Dec 15;173(12):7259-68
references.pmid: 15585848
references.citation: J Immunol. 2005 Mar 1;174(5):2787-95
references.pmid: 15728488
references.citation: Nat Immunol. 2005 Nov;6(11):1142-51
references.pmid: 16227984
references.citation: J Exp Med. 2001 Sep 17;194(6):769-79
references.pmid: 11560993
references.citation: Cell. 1993 Oct 22;75(2):253-61
references.pmid: 8402910
references.citation: J Exp Med. 2002 Dec 16;196(12):1627-38
references.pmid: 12486105
references.citation: J Exp Med. 2007 Jan 22;204(1):191-201
references.pmid: 17210729