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CD8 T-cell response may be associated with tuberculosis in children
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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.
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.
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