title: T lymphocytes from chagasic patients are activated but lack proliferative capacity and down-regulate CD28 and CD3ζ.
abstract: BACKGROUND
  Chronic persistent infections have been associated with T lymphocytes functional impairment. The aim of this study was to compare the activation status, the proliferative potential and the expression of CD28 and CD3ζ chain on T lymphocytes between chronic chagasic patients and uninfected controls.
  
  
  RESULTS
  Forty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included. Peripheral blood was marked for CD3, CD4, CD8, HLA-DR, CD28, CD38 and intracellular CD3ζ. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidylester and incubated with T. cruzi lysate or phytohemagglutinin for five days. Cells from 3 healthy controls were incubated with T. cruzi trypomastigotes separated with transwells; and the expression of CD3ζ chain and proliferation index was determined. Heart-infiltrating cells from two chronic chagasic patients were tested for the aforementioned cellular markers. Chagasic patients displayed higher frequencies of CD4+/HLA-DR+/CD38+ (8.1% ± 6.1) and CD8+/HLA-DR+/CD38+ (19.8 ± 8.9) T cells in comparison with healthy (1.6 ± 1.0; 10.6 ± 8.0) and non-chagasic cardiomyopathy donors (2.9 ± 2.9; 5.8 ± 6.8). Furthermore, the percentage of CD4+ activated T cells was higher in chagasic patients with cardiac involvement. CD8+ T cells proliferation index in chagasic donors (1.7 ± 0.3) was lower when compared with healthy (2.3 ± 0.3) and non-chagasic cardiomyopathy individuals (3.1 ± 1.1). The frequencies of CD4+/CD28+ and CD8+/CD28+ T cells, as well as the CD3ζ(bright)/CD3ζ(dim)% ratios in CD4+ and CD8+ were lower in chagasic patients when compared with both control groups. The CD3ζ(bright)/CD3ζ(dim)% ratio and proliferative indexes for CD4+ and CD8+ T lymphocytes decreased gradually in those cells cultivated with parasites and displayed lower values than those incubated with medium alone. Finally, heart-infiltrating T cells from two T. cruzi infected patients also expressed activation markers and down-regulate CD28 and CD3ζ.
  
  
  CONCLUSIONS
  CD8+ T lymphocytes from chagasic donors displayed reduced proliferative capacity, which might be associated with CD3ζ down-regulation and diminished CD28 expression on CD4 T cells.
authors: Grupo de Ciencias Básicas Médicas, Facultad de Medicina, Universidad de los Andes, Bogotá, Colombia.
authors: Nicolás A
authors: NA
authors: Giraldo
authors: Natalia I
authors: NI
authors: Bolaños
authors: Adriana
authors: A
authors: Cuellar
authors: Nubia
authors: N
authors: Roa
authors: Zulma
authors: Z
authors: Cucunubá
authors: Fernando
authors: F
authors: Rosas
authors: Víctor
authors: V
authors: Velasco
authors: Concepción J
authors: CJ
authors: Puerta
authors: John M
authors: JM
authors: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000096:biosynthesis*; D017252:CD3 Complex / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain
references: J Clin Immunol. 2009 Jul;29(4):532-44
references: 19259799
references: Mem Inst Oswaldo Cruz. 1991 Apr-Jun;86(2):147-52
references: 1842408
references: Cytometry A. 2011 Feb;79(2):95-101
references: 21265003
references: Clin Exp Immunol. 2006 Jul;145(1):81-92
references: 16792677
references: J Biomed Biotechnol. 2010;2010:
references: 20936133
references: J Clin Invest. 1998 Apr 1;101(7):1448-57
references: 9525988
references: PLoS Pathog. 2010 Aug 19;6(8):e1001051
references: 20808900
references: Dev Comp Immunol. 1997 Nov-Dec;21(6):471-8
references: 9463780
references: J Immunol. 2001 Nov 15;167(10):5620-7
references: 11698433
references: Clin Exp Immunol. 2002 Jan;127(1):137-44
references: 11882044
references: J Infect Dis. 2004 Mar 1;189(5):909-18
references: 14976609
references: Parasite Immunol. 2010 Jul;32(7):494-502
references: 20591120
references: Mol Biochem Parasitol. 1998 Apr 1;92(1):133-45
references: 9574917
references: Acta Trop. 2010 Jul-Aug;115(1-2):5-13
references: 20382097
references: Rev Soc Bras Med Trop. 1999 Mar-Apr;32(2):157-65
references: 10228366
references: Blood. 2000 Aug 1;96(3):1021-9
references: 10910918
references: J Virol. 2004 Jun;78(11):5535-45
references: 15140950
references: J Immunol. 1993 Apr 15;150(8 Pt 1):3161-9
references: 7682233
references: Clin Exp Immunol. 2004 Jul;137(1):129-38
references: 15196253
references: J Immunol. 1993 Apr 1;150(7):3070-9
references: 8454874
references: J Virol. 2011 Dec;85(23):12343-50
references: 21937661
references: PLoS Negl Trop Dis. 2009;3(4):e419
references: 19381287
references: J Immunol. 2009 Sep 15;183(6):4103-8
references: 19692645
references: J Immunol. 1983 Feb;130(2):908-11
references: 6401309
references: J Immunol. 1999 Dec 15;163(12):6769-76
references: 10586076
references: AIDS. 1992 Aug;6(8):793-7
references: 1418775
references: J Virol. 2000 Aug;74(16):7320-30
references: 10906185
references: Clin Exp Immunol. 1998 Oct;114(1):78-86
references: 9764607
references: Blood. 2001 Jun 15;97(12):3851-9
references: 11389026
references: Scand J Immunol. 1996 Jan;43(1):88-93
references: 8560201
references: J Immunol. 1990 May 15;144(10):4000-4
references: 2185317
references: Scand J Immunol. 2005 Sep;62(3):297-308
references: 16179017
references: Blood. 2004 Jul 15;104(2):478-86
references: 15044252
references: Am J Trop Med Hyg. 2010 May;82(5):861-4
references: 20439967
references: J Immunol. 1999 Sep 15;163(6):3344-53
references: 10477604
references: PLoS One. 2012;7(5):e35966
references: 22574131
references: PLoS Negl Trop Dis. 2011 Aug;5(8):e1294
references: 21886854
references: Immunology. 2010 Apr;129(4):474-81
references: 20201977
references: J Virol. 2003 Apr;77(8):4911-27
references: 12663797
references: Circulation. 2007 Mar 6;115(9):1124-31
references: 17339570
references: J Acquir Immune Defic Syndr. 2010 Aug;54(5):447-54
references: 20463584
references: J Infect Dis. 2003 Jun 1;187(11):1726-34
references: 12751030
references: Microbes Infect. 2004 Nov;6(13):1133-44
references: 15488732
references: J Infect Dis. 1998 Apr;177(4):1083-7
references: 9534988
references: Int Immunol. 1994 Apr;6(4):499-506
references: 8018591
references: Int Immunol. 2006 Mar;18(3):465-71
references: 16431876
references: Scand J Immunol. 1998 Mar;47(3):254-62
references: 9519864
references: Infect Immun. 1998 Feb;66(2):499-504
references: 9453602
references: Infect Immun. 2003 Jun;71(6):3131-7
references: 12761091
references: Nature. 2003 Feb 20;421(6925):852-6
references: 12594515
references: Cytometry. 1997 Feb 15;30(1):28-32
references: 9056739
references: Rev Med Chil. 2002 Apr;130(4):363-7
references: 12090100
references: Immunol Cell Biol. 2009 Feb;87(2):149-53
references: 18957935
references: J Virol. 2011 Oct;85(19):10252-60
references: 21795350
references: Parasitol Res. 2002 Oct;88(10):894-900
references: 12209329
references: Immunity. 2008 May;28(5):710-22
references: 18468462
references: Virol J. 2010 Nov 12;7:310
references: 21070674