Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV-1 infected individuals in vivo.

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.