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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Compartmentalization of immune responses in human tuberculosis: Few CD8+ effector T cells but elevated levels of FoxP3+ regulatory T cells in the granulomatous lesions
American Journal of Pathology, Volume 174, No. 6, Year 2009
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Description
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. Copyright © American Society for Investigative Pathology.
Authors & Co-Authors
Rahman, Sayma
Sweden, Stockholm
Karolinska Universitetssjukhuset
Gudetta, Berhanu
Ethiopia, Addis Ababa
Addis Ababa University
Fink, Joshua
Sweden, Stockholm
Karolinska Universitetssjukhuset
Granath, Anna
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ashenafi, Senait
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ethiopia, Addis Ababa
Addis Ababa University
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Derbew, Miliard
Ethiopia, Addis Ababa
Addis Ababa University
Svensson, Mattias
Sweden, Stockholm
Karolinska Universitetssjukhuset
Andersson, Jan P.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Brighenti, Susanna Grundström
Sweden, Stockholm
Karolinska Universitetssjukhuset
Statistics
Citations: 33
Authors: 10
Affiliations: 3
Identifiers
Doi:
10.2353/ajpath.2009.080941
e-ISSN:
15252191
Research Areas
Cancer
Maternal And Child Health
Study Approach
Quantitative