CD11c depletion severely disrupts Th2 induction and development in vivo.
Although dendritic cells (DCs) are adept initiators of CD4(+) T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c-diphtheria toxin (DTx) receptor mice to deplete CD11c(+) cells during the priming stage of the CD4(+) Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c(+) DCs from all tissues tested, with 70-80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4(+) T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c(+) antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines.
Phythian-Adams
Alexander T
AT
Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3JT Scotland, UK.
Cook
Peter C
PC
Lundie
Rachel J
RJ
Jones
Lucy H
LH
Smith
Katherine A
KA
Barr
Tom A
TA
Hochweller
Kristin
K
Anderton
Stephen M
SM
Hämmerling
Günter J
GJ
Maizels
Rick M
RM
MacDonald
Andrew S
AS
D000818:Animals; D017951:Antigen Presentation; D001491:Basophils / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D008213:Lymphocyte Activation; D051379:Mice; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D039521:CD11c Antigen; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma
Immunol Rev. 2004 Oct;201:168-79
15361240
Immunity. 2004 May;20(5):623-35
15142530
Immunol Cell Biol. 2010 Mar-Apr;88(3):250-6
20065995
Immunol Rev. 2004 Oct;201:156-67
15361239
Blood. 2006 Oct 1;108(7):2420-7
16772607
Immunity. 2001 Aug;15(2):303-11
11520464
J Exp Med. 2009 Mar 16;206(3):549-59
19237601
J Immunol. 2008 Nov 15;181(10):6697-701
18981085
Immunity. 2009 Sep 18;31(3):412-24
19766084
Nat Rev Immunol. 2002 Jul;2(7):499-511
12094224
Nat Immunol. 2009 Jul;10(7):697-705
19465906
J Immunol. 2010 Feb 1;184(3):1143-7
20038645
J Immunol. 2001 Aug 15;167(4):1982-8
11489979
J Immunol. 2005 Sep 15;175(6):3920-6
16148138
Trends Parasitol. 2009 Dec;25(12):551-6
19782643
Nature. 1998 Mar 19;392(6673):245-52
9521319
J Exp Med. 2008 Jan 21;205(1):13-7
18195077
J Exp Med. 2008 Apr 14;205(4):869-82
18362170
Chem Immunol Allergy. 2006;90:65-81
16210903
Nat Rev Immunol. 2010 Apr;10(4):225-35
20336151
Nat Rev Immunol. 2003 Dec;3(12):984-93
14647480
J Exp Med. 1998 Feb 16;187(4):619-29
9463412
Nat Rev Immunol. 2003 Sep;3(9):733-44
12949497
Annu Rev Immunol. 2009;27:451-83
19105661
Immunol Rev. 2010 Mar;234(1):76-89
20193013
Eur J Immunol. 2008 Oct;38(10):2776-83
18825750
Nat Immunol. 2009 Jul;10(7):706-12
19465908
Int J Parasitol. 2006 May 31;36(6):711-21
16696981
Nat Immunol. 2009 Jul;10(7):713-20
19465907