title: T cells from Programmed Death-1 deficient mice respond poorly to Mycobacterium tuberculosis infection.
abstract: BACKGROUND
  Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.
  
  
  RESULTS
  Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.
  
  
  CONCLUSIONS
  Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice.
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Sultan
authors: S
authors: Tousif
authors: Yogesh
authors: Y
authors: Singh
authors: Durbaka Vijaya Raghava
authors: DV
authors: Prasad
authors: Pawan
authors: P
authors: Sharma
authors: Luc
authors: L
authors: Van Kaer
authors: Gobardhan
authors: G
authors: Das
references: J Immunol. 2009 Jan 15;182(2):980-7
references: 19124741
references: J Exp Med. 2010 Jul 5;207(7):1409-20
references: 20547826
references: J Exp Med. 2007 Sep 3;204(9):2159-69
references: 17709423
references: J Exp Med. 1971 Sep 1;134(3 Pt 1):713-40
references: 15776571
references: J Immunol. 2008 Jul 1;181(1):116-25
references: 18566376
references: Nature. 2010 Jun 10;465(7299):793-7
references: 20535209
references: Curr Top Microbiol Immunol. 2009;335:169-88
references: 19802565
references: J Immunol. 2008 Sep 15;181(6):3741-4
references: 18768824
references: Trends Cell Biol. 2001 Dec;11(12):526-34
references: 11719060
references: Annu Rev Nutr. 2007;27:19-40
references: 17311494
references: Eur J Immunol. 2006 Jan;36(1):58-64
references: 16358363
references: N Engl J Med. 2003 Sep 18;349(12):1149-56
references: 13679530
references: Nature. 2006 Feb 9;439(7077):682-7
references: 16382236
references: Immunol Rev. 2005 Apr;204:128-43
references: 15790355
references: Clin Infect Dis. 2010 May 15;50 Suppl 3:S245-54
references: 20397955
references: Nat Rev Immunol. 2005 Oct;5(10):819-26
references: 16200083
references: J Immunol Methods. 1992 Sep 18;154(1):1-6
references: 1401935
references: Annu Rev Immunol. 2008;26:677-704
references: 18173375
references: Cell. 2008 Jan 11;132(1):27-42
references: 18191218
references: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21653-8
references: 21135221
references: Immunity. 2009 Dec 18;31(6):974-85
references: 20064452
references: J Exp Med. 2001 Apr 2;193(7):839-46
references: 11283156
references: J Immunol. 2010 Apr 15;184(8):4414-22
references: 20212094
references: Int Immunol. 2004 Aug;16(8):1181-8
references: 15237109
references: J Clin Invest. 2009 Jan;119(1):61-9
references: 19075395
references: Cell Microbiol. 2006 May;8(5):719-27
references: 16611222
references: Curr Opin Immunol. 2010 Jun;22(3):397-401
references: 20427170
references: Curr Opin Immunol. 2006 Aug;18(4):375-82
references: 16782319
references: Cell. 2004 Dec 17;119(6):753-66
references: 15607973
references: Curr Opin Immunol. 2007 Jun;19(3):309-14
references: 17433872
references: Nat Med. 2006 Oct;12(10):1198-202
references: 16917489
references: Immunity. 2007 Jul;27(1):111-22
references: 17629517
references: Nature. 2009 Mar 12;458(7235):206-10
references: 19078956
references: J Biol Chem. 2004 May 21;279(21):22477-82
references: 15037612
references: J Exp Med. 1993 Dec 1;178(6):2249-54
references: 7504064
references: J Clin Invest. 2007 Oct;117(10):2974-82
references: 17853943
references: J Exp Med. 1993 Dec 1;178(6):2243-7
references: 8245795
references: Immunity. 2007 Sep;27(3):505-17
references: 17892853
references: Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13402-7
references: 20624978
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10691-6
references: 15249675
references: Annu Rev Immunol. 2001;19:93-129
references: 11244032
references: JAMA. 1999 Aug 18;282(7):677-86
references: 10517722
references: J Immunol. 2005 Dec 1;175(11):7372-9
references: 16301644
references: Nat Immunol. 2007 Mar;8(3):239-45
references: 17304234
references: J Immunol. 2011 Feb 1;186(3):1598-607
references: 21172867
references: Eur J Immunol. 2005 Dec;35(12):3561-9
references: 16278812
references: Nat Immunol. 2001 Mar;2(3):261-8
references: 11224527