ArticleImmunology2002
Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas.
Article in Immunology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 90 citations in OpenAlex.
- Immunopathogenesis of tuberculosis: cellular mechanisms and immune modulation.Veterinary research · 2025Review
- Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications.Nature communications · 2025Article
- Article
- LAG3 expression in active Mycobacterium tuberculosis infections.The American journal of pathology · 2015Article
- Macrophages in tuberculosis: friend or foe.Seminars in immunopathology · 2013Review
- Immunohistological characterization of spinal TB granulomas from HIV-negative and -positive patients.Tuberculosis (Edinburgh, Scotland) · 2013Article
- Kinetics of IFN-gamma and TNF-alpha gene expression and their relationship with disease progression after infection with Mycobacterium tuberculosis in guinea pigs.Yonsei medical journal · 2013Article
- Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum.PloS one · 2013Article
- Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2012Article
- Cellular and humoral mechanisms involved in the control of tuberculosis.Clinical & developmental immunology · 2012Review
- Immunodiagnosis of tuberculosis: a dynamic view of biomarker discovery.Clinical microbiology reviews · 2011Review
- Indoleamine 2,3-dioxygenase, tryptophan catabolism, and Mycobacterium avium subsp. paratuberculosis: a model for chronic mycobacterial infections.Infection and immunity · 2011Article
- Compartmentalization of immune responses in human tuberculosis: few CD8+ effector T cells but elevated levels of FoxP3+ regulatory t cells in the granulomatous lesions.The American journal of pathology · 2009Article
- Th1-Th2 polarisation and autophagy in the control of intracellular mycobacteria by macrophages.Veterinary immunology and immunopathology · 2009Article
- Pleural tuberculosis in patients with early HIV infection is associated with increased TNF-alpha expression and necrosis in granulomas.PloS one · 2009Article
- Inflammation and structural changes of splenic lymphoid tissue in visceral leishmaniasis: a study on naturally infected dogs.Parasite immunology · 2008Article
- Cytokine mRNA expression in Mycobacterium ulcerans-infected human skin and correlation with local inflammatory response.Infection and immunity · 2006Article
- Cytokine expression profiles of bovine lymph nodes: effects of Mycobacterium bovis infection and bacille Calmette-Guérin vaccination.Clinical and experimental immunology · 2006Article
- Mycobacterium tuberculosis-specific CD8+ T cells and their role in immunity.Critical reviews in immunology · 2006Review
- Influence of pathological progression on the balance between cellular and humoral immune responses in bovine tuberculosis.Immunology · 2005Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to examine the immune response at the site of pathology in tuberculosis, we analysed cytokines present in lung granulomas, their associations with each other and with caseous necrosis as well as the phenotype of the cellular infiltrate. Paraffin-embedded tissue from the lungs of seven patients with pulmonary tuberculosis was analysed by immunohistochemistry and in situ hybridization to detect interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) proteins and IL-12p40 mRNA. All seven patients had granulomas staining positive for IFN-gamma, TNF-alpha and IL-12p40, but only four stained positive for IL-4. Cells with the morphology of lymphocytes, macrophages and giant cells expressed TNF-alpha, IFN-gamma and IL-4 protein. Furthermore, CD68-positive myeloid cells expressed IL-12p40 mRNA, as expected, but a subset of CD3-positive lymphocytes also expressed this mRNA. These lymphocytes producing IL-12p40 also stained positive for CD8 but not CD4. A total of 141 granulomas were scored for the presence or absence of cytokine or necrosis and two major associations were identified. The first association was between IFN-gamma and IL-12, with 76% of granulomas staining positive for both cytokines. Unexpectedly, those granulomas positive for IL-4 were always positive for IFN-gamma. The second association was between TNF-alpha and caseous necrosis, where all necrotic granulomas were TNF-alpha positive. This association was modulated by IL-4. Therefore, heterogeneity of cellular infiltrate and cytokine expression is observed between adjacent granulomas in the same patient.
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