title: Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas.
abstract: Cell-mediated adaptive immunity is critical for host defense, but little is known about T cell behavior during delivery of effector function. Here we investigate relationships among antigen presentation, T cell motility, and local production of effector cytokines by CD4+ T cells within hepatic granulomas triggered by Bacille Calmette-Guérin or Mycobacterium tuberculosis. At steady-state, only small fractions of mycobacteria-specific T cells showed antigen-induced migration arrest within granulomas, resulting in low-level, polarized secretion of cytokines. However, exogenous antigen elicited rapid arrest and robust cytokine production by the vast majority of effector T cells. These findings suggest that limited antigen presentation and/or recognition within granulomas evoke a muted T cell response drawing on only a fraction of the host's potential effector capacity. Our results provide new insights into the regulation of host-protective functions, especially how antigen availability influences T cell dynamics and, in turn, effector T cell function during chronic infection.
authors: Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jackson G
authors: JG
authors: Egen
authors: Antonio Gigliotti
authors: AG
authors: Rothfuchs
authors: Carl G
authors: CG
authors: Feng
authors: Marcus A
authors: MA
authors: Horwitz
authors: Alan
authors: A
authors: Sher
authors: Ronald N
authors: RN
authors: Germain
references: J Immunol. 1999 May 1;162(9):5407-16
references: 10228018
references: Nature. 2004 Jan 8;427(6970):154-9
references: 14712275
references: Nature. 2009 Jan 8;457(7226):191-5
references: 19011611
references: Nat Immunol. 2008 Mar;9(3):282-91
references: 18204450
references: Infect Immun. 1994 Feb;62(2):363-70
references: 7507889
references: J Exp Med. 2003 Mar 17;197(6):751-62
references: 12629067
references: Blood. 2005 Sep 1;106(5):1843-50
references: 15886329
references: J Immunol. 2009 May 15;182(10):6379-93
references: 19414791
references: Eur J Immunol. 1995 Feb;25(2):377-84
references: 7875199
references: Science. 2006 Apr 7;312(5770):114-6
references: 16513943
references: Science. 2002 Jun 7;296(5574):1873-6
references: 12052961
references: Int Immunol. 2004 Dec;16(12):1691-9
references: 15477229
references: Immunol Cell Biol. 2007 Feb-Mar;85(2):103-11
references: 17213830
references: Nat Immunol. 2007 Aug;8(8):835-44
references: 17632517
references: Nat Immunol. 2003 Jun;4(6):579-85
references: 12730692
references: J Exp Med. 2004 Oct 4;200(7):847-56
references: 15466619
references: J Pathol. 2006 Jan;208(2):261-9
references: 16362982
references: Immunol Cell Biol. 1998 Feb;76(1):34-40
references: 9553774
references: PLoS One. 2010 Jul 06;5(7):e11453
references: 20625513
references: Immunity. 2009 Feb 20;30(2):300-11
references: 19167248
references: Cell. 2009 Jan 9;136(1):37-49
references: 19135887
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13853-8
references: 11095745
references: Mol Cell Biol. 2008 Jun;28(12):4040-51
references: 18426917
references: Nat Rev Microbiol. 2010 Apr;8(4):296-307
references: 20234378
references: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4553-8
references: 17360562
references: Trends Immunol. 2005 Mar;26(3):136-40
references: 15745855
references: J Exp Med. 2001 Feb 5;193(3):271-80
references: 11157048
references: Immunity. 2008 Oct 17;29(4):602-14
references: 18835197
references: PLoS Pathog. 2010 Mar 12;6(3):e1000805
references: 20300603
references: Cell Immunol. 2001 Dec 15;214(2):110-22
references: 12088410
references: Science. 2002 Jun 7;296(5574):1869-73
references: 12016203
references: Cell Host Microbe. 2009 Jul 23;6(1):23-33
references: 19616763
references: Immunol Cell Biol. 2007 Jun;85(4):306-14
references: 17420768
references: J Immunol. 2008 Feb 1;180(3):1344-52
references: 18209028
references: Annu Rev Immunol. 2001;19:93-129
references: 11244032
references: Nat Immunol. 2009 Nov;10(11):1185-92
references: 19783989
references: Immunity. 2008 Feb;28(2):271-84
references: 18261937
references: Nat Rev Immunol. 2008 Sep;8(9):675-84
references: 19172690
references: Nature. 2009 Nov 5;462(7269):94-8
references: 19829296
references: J Exp Med. 2008 Jan 21;205(1):105-15
references: 18158321
references: J Exp Med. 2005 Jun 6;201(11):1805-14
references: 15939794
references: J Exp Med. 2005 Nov 7;202(9):1271-8
references: 16275764
references: Blood. 2000 Jul 15;96(2):719-26
references: 10887140