Host Responses and Antigens Involved in Protective Immunity to <i>Mycobacterium tuberculosis</i>

Andersen, Peter

doi:10.1046/j.1365-3083.1997.d01-380.x

Cited by 159 publications

(117 citation statements)

References 173 publications

(259 reference statements)

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“…Irradiated splenocytes from uninfected B6 mice were used as APCs at a concentration of 1 ϫ 10 6 cells/well in all wells. The relatively immunodominant (4% of CD4 ϩ T cells in infected lungs) Mtb ESAT-6 1-20 peptide (10 g/ml) (22,23) was used as the Ag for assays from infected mice, whereas the OVA peptide was used to stimulate cells from OT-II ␣␤TCR-transgenic mice; mouse rIL-2 (Sigma-Aldrich; 10 U/ml) was added to all wells. After 24 h of incubation in 5% CO 2 at 37°C, the plates were washed, and biotinylated anti-mouse IFN-␥ (clone XMG1.2; eBiosciences) or biotinylated anti-mouse IL-17 Ab (clone AUS02; R&D Systems) was used to detect the captured cytokine.…”

Section: Detection Of Ifn-␥-and Il-17-producing Cells By Elispot Assaymentioning

confidence: 99%

IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available

Khader

Pearl

Sakamoto

et al. 2005

The Journal of Immunology

418

457

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IL-12p70 induced IFN-γ is required to control Mycobacterium tuberculosis growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway mediates induction of IFN-γ and initial bacteriostatic activity. IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation. We show that in IL-23 p19-deficient mice, mycobacterial growth is controlled, and there is no diminution in either the number of IFN-γ-producing Ag-specific CD4 T cells or local IFN-γ mRNA expression. Conversely, there is an almost total loss of both IL-17-producing Ag-specific CD4 T cells and local production of IL-17 mRNA in these mice. The absence of IL-17 does not alter expression of the antimycobacterial genes, NO synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are implicated in mediating inflammation, fails to substantially affect the granulomatous response to M. tuberculosis infection of the lung. Despite this redundancy, IL-23 is required to provide a moderate level of protection in the absence of IL-12p70, and this protection correlates with a requirement for IL-23 in the IL-12p70-independent induction of Ag-specific, IFN-γ-producing CD4 T cells. We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo.

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Section: Detection Of Ifn-␥-and Il-17-producing Cells By Elispot Assaymentioning

confidence: 99%

IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available

Khader

Pearl

Sakamoto

et al. 2005

The Journal of Immunology

418

457

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“…BCG has been administered by an intradermal route to more than 70% of children worldwide in the last 70 years (2,14), but it has had little impact on the prevalence of TB (13). Several reasons have been advanced to explain the variable efficacy of BCG against pulmonary TB, including the dose of immunization (23), the strain of BCG used (21,22), and the confounding effect of prior exposure to environmental mycobacteria (8).…”

mentioning

confidence: 99%

Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of PriorMycobacterium bovisBCG Immunization

et al. 2002

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“…Since cellular responses are the major immune mechanism in tuberculosis, T-cell reactivity toward well-characterized mycobacterial antigens has been extensively studied (5,12,13). However, the direct screening of antigens with immune cells is technically much more complicated compared to antigen-antibody interactions.…”

Section: Discussionmentioning

confidence: 99%

Identification of Mycobacterium bovis antigens by analysis of bovine T-cell responses after infection with a virulent strain

Alito¹,

McNair

Girvin

et al. 2003

Braz J Med Biol Res

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Purification and characterization of individual antigenic proteins are essential for the understanding of the pathogenic mechanisms of mycobacteria and the immune response against them. In the present study, we used anion-exchange chromatography to fractionate cell extracts and culture supernatant proteins from Mycobacterium bovis to identify T-cell-stimulating antigens. These fractions were incubated with peripheral blood mononuclear cells (PBMC) from M. bovis-infected cattle in lymphoproliferation assays. This procedure does not denature proteins and permits the testing of mixtures of potential antigens that could be later identified. We characterized protein fractions with high stimulation indices from both culture supernatants and cell extracts. Proteins were identified by two-dimensional gel electrophoresis followed by N-terminal sequencing or MALDI-TOF. Culture supernatant fractions containing low molecular weight proteins such as ESAT6 and CFP10 and other proteins (85B, MPB70), and the novel antigens TPX and TRB-B were associated with a high stimulation index. These results reinforce the concept that some low molecular weight proteins such as ESAT6 and CFP10 play an important role in immune responses. Also, Rv3747 and L7/L12 were identified in high stimulation index cell extract fractions. These data show that protein fractions with high lymphoproliferative activity for bovine PBMC can be characterized and antigens which have been already described and new protein antigens can also be identified in these fractions.

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Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

Cited by 159 publications

References 173 publications

IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available

IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available

Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of PriorMycobacterium bovisBCG Immunization

Identification of Mycobacterium bovis antigens by analysis of bovine T-cell responses after infection with a virulent strain

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