Children with tuberculosis have CD8 T-cell responses to Mycobacterium
tuberculosis, whereas young healthy children who have been exposed to
tuberculosis do not, according to research.
The research also showed that TB and young age are not associated with
diminished T-cell responses, and healthy exposed children and children with TB
have good T-cell responses to M. tuberculosis.
“Children are uniquely vulnerable to TB,” said study
researcher Christina Lancioni, MD, of the Oregon Health and Science
University in Portland, Oregon. “Our data show that [M.
tuberculosis]-stimulated CD8 T cells identify young children with TB. This
observation may have implications for development of improved TB diagnostics in
children.”
Lancioni and colleagues conducted a cross-sectional study that included
82 healthy children aged 0 to 15 years in Uganda who had exposure to an adult
with confirmed TB and 96 hospitalized children aged 0 to 10 years with
confirmed TB. They sought out to determine if M. tuberculosis-specific
CD4 and CD8 T-cell response varied by age among the healthy children. They also
evaluated whether deficient M. tuberculosis-specific CD4 and CD8 T-cell
responses are associated with TB. They measured interferon-gamma-producing CD4
T cells and interferon-gamma-producing CD8 T cells. The cells were stimulated
with synthetic M. tuberculosis-specific proteins.
All of the children — those with TB and those with TB exposure
— had strong CD4 T-cell responses. Twenty-five healthy children aged
younger than 5 years had decreased M. tuberculosis-specific CD8 T cells
compared with 34 healthy children aged 5 to 15 years (P=.055). Children
with TB also demonstrated strong CD8 T-cell responses compared with contacts
(P=.01). The proportion of positive CD8 T-cell assays was greater in TB
cases than in contacts (P=.007). In a multivariate analysis, children
with CD8 T-cell responses to M. tuberculosis had significantly greater
odds of having TB compared with the contacts (P=.005).
Lancioni C. #1165.3.
Disclosure: Dr. Lancioni reports no relevant financial
disclosures.
Dr. Jeffrey D. Starke
This study is an excellent step in better defining the
immunologic responses of children to tuberculosis. As with all good preliminary
studies, it leads to more questions than the ones it attempts to answer. One
limitation of this study is that the “tuberculosis exposed” group
– as presented at the meeting – was really made up of two groups:
children who were recently infected with Mycobacterium tuberculosis and
those who were exposed but not infected. Hopefully, upon further analysis of
the data, the authors can distinguish between these groups, as important
differences may exist. The accurate diagnosis of tuberculosis in children has
been an elusive target. Cultures are positive less than 50% of the time, PCR
has added little, and the tests for infection with M. tuberculosis [the
tuberculin skin test and the interferon-gamma release asays] are notoriously
inaccurate. So much of the clinical and radiographic presentation of
tuberculosis in children depends on the child’s immune response to the
organism. While CD8 cell counts alone are not likely to significantly improve
diagnosis, they likely are an important piece of the puzzle.
These studies also may have important implications for
new tuberculosis vaccine development. Whatever parts of the immune system that
are “turned-on” or “turned-off” by a vaccine may determine
the vaccine’s effectiveness and the clinical expression of the interaction
between the child and the organism after vaccination. Some vaccines could
actually make subsequent tuberculosis worse by changing the immune response.
Only through studies such as this one will we come to understand the nature of
the natural immune response so we can manipulate it effectively to prevent
childhood tuberculosis.
– Jeffrey R. Starke, MD
Infectious Diseases in Children Editorial Board
member
Disclosure: Dr. Starke reports no relevant
financial disclosures.