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Ligand-specific alphabeta and gammadelta T cell responses in childhood tuberculosis
1Institute of General Pathology, University of Palermo, Palermo, Italy.
Insights
Childhood tuberculosis (TB) involves distinct T cell responses. While alphabeta T cells react to purified protein derivative (PPD), Vgamma9/Vdelta2 T cells show altered phosphoantigen responses in active TB patients.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Tuberculosis (TB) remains a significant global health challenge, particularly in children.
- Understanding T cell responses in pediatric TB is crucial for diagnosis and treatment.
- Distinct T cell subsets, including alphabeta and gammadelta T cells, play roles in immune responses to Mycobacterium tuberculosis.
Purpose of the Study:
- To investigate and compare alphabeta and gammadelta T cell responses in children with active TB versus healthy controls.
- To assess the response to purified protein derivative (PPD) and specific Mycobacterium tuberculosis antigens.
- To evaluate the impact of chemotherapy on T cell populations in pediatric TB.
Main Methods:
- Analysis of peripheral blood T cell responses (alphabeta and gammadelta) in children with active TB and healthy controls (PPD+ and PPD-).
- In vitro stimulation assays using PPD, peptide p38G (from Mycobacterium tuberculosis), and phosphoantigens.
- Flow cytometry to analyze T cell frequencies and subsets (Vgamma9/Vdelta2).
Main Results:
- Children with active TB and healthy PPD+ children showed similar responses to PPD.
- A low percentage (18%) of PPD+ TB patients responded to the p38G peptide.
- Vgamma9/Vdelta2 T cell frequencies were similar across all groups, but their phosphoantigen response was impaired in active TB and healthy PPD- children.
- Chemotherapy increased alphabeta T cell responses while decreasing Vgamma9/Vdelta2 responses.
Conclusions:
- Childhood TB exhibits specific T cell response patterns, with impaired Vgamma9/Vdelta2 T cell reactivity to phosphoantigens.
- The findings suggest potential similarities between T cell responses in childhood and adult TB.
- Chemotherapy significantly alters T cell dynamics in pediatric TB patients.
Abstract:
The alphabeta and gammadelta T cell responses were analyzed in the peripheral blood of children affected by active tuberculosis (TB) and in healthy children who tested positive (PPD+) or negative (PPD-) for purified protein derivative. PPD+ healthy and diseased children responded equally well to PPD in vitro. In contrast, only 18% of PPD+ TB patients responded to peptide p38G derived from the 38-kDa protein of Mycobacterium tuberculosis. Analysis of the whole gammadelta T cell population and of its Vgamma9/Vdelta2 subset showed similar frequencies in PPD+ children with TB and in healthy PPD+ and PPD- children. Vgamma9/Vdelta2 cells from children with TB responded to 5 different phosphoantigens similarly to those from healthy PPD+ children, but healthy PPD- children responded very poorly. Chemotherapy had contrasting effects on the tested lymphocyte population, represented by increase of alphabeta and decline of Vgamma9/Vdelta2 T cell responses. T cell responses in childhood TB may be similar to those in adult TB.