Diversity of Lung and Spleen Immune Responses in Mice with Slowly Progressive Primary Tuberculosis

Phyu,; Mustafa,; Tadesse,; Jønsson,; Bjune,

doi:10.1046/j.1365-3083.2000.00662.x

Cited by 2 publications

(3 citation statements)

References 42 publications

(62 reference statements)

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“…Furthermore, a more pronounced diversity was observed in the Ag recognition by autologous PBMCs and BAL cells of minimal TB patients. Nonetheless, the disparity between spleen and lung immune responses in mice [21,22], as well as between PBMCs and BAL cell responses in humans using few characterised Ags like ESAT-6 and Ag85 complex proteins, have been reported previously [9,10]. This is consistent with the observation made in the present study.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, detectable in vitro IL-12 (p40) responses to Ag85 complex proteins only were also observed in BAL cells of minimal TB patients. In fact, Ag85A and B proteins had already been demonstrated as suitable candidates for the development of future antituberculous vaccine [21,[29][30][31]. Predominant recognition of these proteins by BAL cells, characterised by prominent release of IL-12, IFN-c and NO in vitro, suggests the potential of these Ags as constituents of a future mucosal anti-TB vaccine.…”

Section: Discussionmentioning

confidence: 99%

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Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins

Sable¹,

Goyal²,

Verma³

et al. 2006

European Respiratory Journal

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The differences in specificity of human lung and peripheral lymphocytes for mycobacterial antigens (Ag) need to be evaluated in order to identify vaccine candidates against pulmonary tuberculosis (TB).Therefore, the present study examined the response to low molecular weight secretory proteins of Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) from minimal pulmonary TB and non-TB patients.Ag85A, Ag85B, culture filtrate protein (CFP)-31, CFP-22.5, CFP-21, M. tuberculosis protein-64 and an as yet uncharacterised 19 kDa protein were found to be predominantly recognised by BAL cells of TB patients on the basis of lymphocyte proliferation and significant interferon-c release. However, recognition of CFP-8, 6-kDa early secreted antigenic target, CFP-10, CFP-14.5, M. tuberculosis secretory protein-17 and five other as yet uncharacterised low molecular weight polypeptides was found to be high on the basis of lymphocyte proliferation at the level of PBMCs. Furthermore, BAL macrophages, and not blood monocytes, were found to produce nitric oxide (NO) in response to mycobacterial Ags. Among polypeptides predominantly recognised by BAL lymphocytes, only Ag85A and Ag85B were found to induce both NO and interleukin-12 (p40) by alveolar macrophages.In conclusion, the present results indicate heterogeneity in antigen recognition by bronchoalveolar lavage cells and peripheral mononuclear blood cells of minimal tuberculosis patients, and also suggest the utility of antigen 85 complex polypeptides for the development of a future mucosal antituberculous vaccine.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins

Sable¹,

Goyal²,

Verma³

et al. 2006

European Respiratory Journal

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“…There was no signi®cant change in the number of TNF-aexpressing cells in phase 3 as compared to phase 2. The lung cells from these mice produced high levels of IFN-g [49]. Despite the presence of TNF-a and IFN-g, which contribute to protection [20±22, 30], there was progression of disease.…”

Section: Discussionmentioning

confidence: 99%

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

Mustafa

Phyu²,

Nilsen³

et al. 2000

Scand J Immunol

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51:548±556The cellular phenotypes and the expression of cytokines were studied in the lungs of mice, using immunohistochemistry, during different phases of slowly progressive primary murine tuberculosis infection. During the ®rst phase the small focal lesions in healthy mice contained predominantly interleukin-2 (IL-2)-expressing cells. A small number of tumour necrosis factor-a (TNF-a)-, monocyte chemoattractant protein-1 (MCP-1)-and IL-10-expressing cells were also present. IL-4-expressing cells were not detected. During the second phase the mice became unwell, but the bacterial counts and the size of focal lesions stabilized. IL-4-expressing cells appeared. The IL-10-, TNF-a-and MCP-1-expressing cells increased in number. On progression to phase three, the mice became seriously unwell and died rapidly. The in¯ammation spread to < 80% of the lung parenchyma. There was a marked increase in the number of IL-10-expressing cells. Expression of other cytokines was similar to that observed in the second phase. In the lesions, 3±6% of the macrophages (Mf) containing mycobacterial antigens expressed high levels of IL-10 and TNF-a. The absolute numbers of CD3-, CD4-and CD11b-expressing cells in the lesions increased with the progression of infection. The numbers of CD8 cells were reduced in the last phase of infection. The kinetics of T-lymphocyte subsets and the pattern of cytokine expression changed with the type and degree of tissue injury. The small number of Mf with a heavy load of mycobacterial antigens may be the cause of this disturbance in cytokine balance, thus leading to progression of in¯ammation.

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Diversity of Lung and Spleen Immune Responses in Mice with Slowly Progressive Primary Tuberculosis

Cited by 2 publications

References 42 publications

Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins

Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

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