title: Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV-1 infected individuals in vivo.
abstract: The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNγ). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27(-) phenotype was associated with active TB in HIV(-) (p = 0.0003) and HIV(+) (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV(-) subjects, MTB-specific CD4 T cell populations from HIV(+) TB-asymptomatic subjects were often dominated by CD27(-) cells. These data indicate that down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease. Furthermore, these data are consistent with the hypothesis that late, chronic HIV infection is frequently associated with increased mycobacterial activity in vivo. The analysis of T cell maturation and activation markers might thus be a useful tool to monitor TB disease progression.
authors.affiliation: NIMR-Mbeya Medical Research Programme, Referral Hospital, Mbeya, Tanzania. alexandra.schuetz@afrims.org
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.forename: Antelmo
authors.initials: A
authors.lastname: Haule
authors.forename: Klaus
authors.initials: K
authors.lastname: Reither
authors.forename: Njabulo
authors.initials: N
authors.lastname: Ngwenyama
authors.forename: Andrea
authors.initials: A
authors.lastname: Rachow
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.forename: Leonard
authors.initials: L
authors.lastname: Maboko
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.forename: Christof
authors.initials: C
authors.lastname: Geldmacher
mesh_terms: D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000382:microbiology*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D009169:Mycobacterium tuberculosis; D014376:Tuberculosis / Q000175:diagnosis*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma
references.citation: Lancet. 2006 Nov 4;368(9547):1575-80
references.pmid: 17084757
references.citation: J Exp Med. 2010 Dec 20;207(13):2869-81
references.pmid: 21115690
references.citation: AIDS. 1993 Jul;7(7):981-7
references.pmid: 8357557
references.citation: AIDS. 2000 Dec 1;14(17):2653-60
references.pmid: 11125883
references.citation: AIDS. 2006 Feb 28;20(4):609-15
references.pmid: 16470126
references.citation: AIDS. 2002 Nov 22;16(17):2285-93
references.pmid: 12441800
references.citation: Eur J Immunol. 2009 Aug;39(8):2076-82
references.pmid: 19672903
references.citation: J Immunol. 2007 Jan 15;178(2):976-85
references.pmid: 17202360
references.citation: Nat Rev Microbiol. 2009 Dec;7(12):845-55
references.pmid: 19855401
references.citation: JAMA. 1992 Jan 15;267(3):369-73
references.pmid: 1727959
references.citation: J Exp Med. 2008 Sep 29;205(10):2359-68
references.pmid: 18779346
references.citation: AIDS. 2007 Nov;21 Suppl 6:S97-S104
references.pmid: 18032945
references.citation: Curr Opin Pulm Med. 2009 May;15(3):188-200
references.pmid: 19387262
references.citation: J Immunol Methods. 2006 Jun 30;313(1-2):199-208
references.pmid: 16756987
references.citation: PLoS One. 2007 Aug 15;2(8):e735
references.pmid: 17710135
references.citation: J Infect Dis. 2008 Dec 1;198(11):1590-8
references.pmid: 19000013