Compartmentalization of Immune Responses in Human Tuberculosis : Few CD8+ Effector T Cells but Elevated Levels of FoxP3+ Regulatory T Cells in the Granulomatous Lesions
AUTOR(ES)
Rahman, Sayma
FONTE
American Society for Investigative Pathology
RESUMO
Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-γ, tumor necrosis factor-α, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-β and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-β and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2684186Documentos Relacionados
- Altered homeostasis of CD4+ FoxP3+ regulatory T-cell subpopulations in systemic lupus erythematosus
- Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas
- Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells
- Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas
- CD4+ CD25high Foxp3+ regulatory T cells downregulate human Vδ2+ T-lymphocyte function triggered by anti-CD3 or phosphoantigen