title: Inoculation dose of Mycobacterium tuberculosis does not influence priming of T cell responses in lymph nodes.
abstract: The effect of Mycobacterium tuberculosis inocula size on T cell priming in the lymph node and effector T cells in the lung remains controversial. In this study, we used a naive mouse model, without the transfer of transgenic T cells, in conjunction with mathematical model to test whether infection with higher aerosolized inocula would lead to increased priming of M. tuberculosis-specific T cells in the lung-draining lymph node. Our data do not support that inoculum size has a measurable influence on T cell priming in the lymph nodes but is associated with more cells overall in the lung, including T cells. To account for increased T cells in the lungs, we tested several possible mechanisms, and recruitment of T cells to the lungs was most influenced by inoculum dose. We also identified IL-10 as a possible mechanism to explain the lack of influence of inoculum dose on priming of T cells in the lymph node.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Myers
authors.forename: Simeone
authors.initials: S
authors.lastname: Marino
authors.forename: Denise E
authors.initials: DE
authors.lastname: Kirschner
authors.forename: JoAnne L
authors.initials: JL
authors.lastname: Flynn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma
references.citation: Immunity. 2003 Dec;19(6):823-35
references.pmid: 14670300
references.citation: Tuberculosis (Edinb). 2009 Mar;89(2):149-57
references.pmid: 19213603
references.citation: J Immunol. 2001 Apr 1;166(7):4312-8
references.pmid: 11254683
references.citation: J Immunol. 2001 Feb 1;166(3):1951-67
references.pmid: 11160244
references.citation: Mucosal Immunol. 2011 May;4(3):261-70
references.pmid: 21451501
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11246-51
references.pmid: 19549875
references.citation: J Theor Biol. 2004 Apr 21;227(4):463-86
references.pmid: 15038983
references.citation: J Immunol. 2004 Mar 1;172(5):2748-51
references.pmid: 14978073
references.citation: J Theor Biol. 2004 Dec 7;231(3):357-76
references.pmid: 15501468
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10961-6
references.pmid: 18667699
references.citation: Annu Rev Immunol. 2009;27:393-422
references.pmid: 19302046
references.citation: Immunology. 2003 Jun;109(2):295-9
references.pmid: 12757625
references.citation: Infect Immun. 2009 Oct;77(10):4621-30
references.pmid: 19667047
references.citation: Exp Cell Res. 1990 Mar;187(1):111-8
references.pmid: 1967582
references.citation: J Theor Biol. 2008 Sep 7;254(1):178-96
references.pmid: 18572196
references.citation: Nat Immunol. 2009 Sep;10(9):929-32
references.pmid: 19692989
references.citation: J Theor Biol. 2010 Aug 21;265(4):586-98
references.pmid: 20510249
references.citation: Eur J Immunol. 2010 Jun;40(6):1663-73
references.pmid: 20222088
references.citation: Infect Immun. 2002 Aug;70(8):4501-9
references.pmid: 12117962
references.citation: J Exp Med. 2008 Jan 21;205(1):105-15
references.pmid: 18158321
references.citation: J Immunol. 2005 Jul 15;175(2):1107-17
references.pmid: 16002712