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Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis.

Poyntz HC, Stylianou E, Griffiths KL, Marsay L, Checkley AM, McShane H - Tuberculosis (Edinb) (2014)

Bottom Line: The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations.CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy.BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection.

View Article: PubMed Central - PubMed

Affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: hpoyntz@malaghan.org.nz.

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Cellular responses in BCG vaccinated mice that were or were not sensitised with MA 724 IP after BCG Responses were assayed at the 12 month time point; 4 weeks after the last dose of MA 724. Cells from inguinal lymph nodes (LN) and spleens were stimulated with PPD-T. (A) Experiment plan (B and C) IFNγ, TNFα and IL-2 production from CD4+ or CD8+ T cells in the LN, (D) IL-17 production from CD4+ T cells in the LN and spleen, (E) IL-4 production from CD4+ T cells in the LN and spleen, (F) expression of CD25, FoxP3 and CD39 on CD4+ T cells from the LN and spleen, (G) IL-10 production from CD4+ T cells in the LN and spleen. B = BCG vaccinated only, BM = BCG vaccinated mice which received MA 724. Results are expressed as a percentage of the CD4+ or CD8+ T cell population and are stimulation specific; media only control well values are subtracted. Each data point represents one mouse and the median is displayed, n = 5. The Mann–Whitney U test was used to determine statistical significance and is shown where differences were significant. Subcutaneous (Sub Cut.), Intraperitoneal (IP), M. avium (MA), Colony Forming Units (CFU), Day 0 (D0), Regulatory T cells (Tregs).
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fig1: Cellular responses in BCG vaccinated mice that were or were not sensitised with MA 724 IP after BCG Responses were assayed at the 12 month time point; 4 weeks after the last dose of MA 724. Cells from inguinal lymph nodes (LN) and spleens were stimulated with PPD-T. (A) Experiment plan (B and C) IFNγ, TNFα and IL-2 production from CD4+ or CD8+ T cells in the LN, (D) IL-17 production from CD4+ T cells in the LN and spleen, (E) IL-4 production from CD4+ T cells in the LN and spleen, (F) expression of CD25, FoxP3 and CD39 on CD4+ T cells from the LN and spleen, (G) IL-10 production from CD4+ T cells in the LN and spleen. B = BCG vaccinated only, BM = BCG vaccinated mice which received MA 724. Results are expressed as a percentage of the CD4+ or CD8+ T cell population and are stimulation specific; media only control well values are subtracted. Each data point represents one mouse and the median is displayed, n = 5. The Mann–Whitney U test was used to determine statistical significance and is shown where differences were significant. Subcutaneous (Sub Cut.), Intraperitoneal (IP), M. avium (MA), Colony Forming Units (CFU), Day 0 (D0), Regulatory T cells (Tregs).

Mentions: Frozen aliquots of bacteria were thawed and sonicated. Where MA was to be given heat-killed, the aliquots were placed in a water bath at 80 °C for 25 min. Bacteria were then diluted to the required concentration in sterile PBS before administration. 100 μl of BCG in PBS was injected subcutaneously (SC) at the base of the tail using a U-100 29G syringe. 1 × 105 CFU was administered. 100 μl of MA 724 or 2-151 for intraperitoneal injection (IP) was suspended in PBS and administered with a U-100 29G syringe in the right or left side of the peritoneal cavity. In the IP exposure model 1 × 108 CFU of killed MA strain 2-151 or 724 were administered. In the model of oral exposure mice received 100 μl of live MA 104 suspended in PBS via a dosing cannula inserted directly in to the stomach. 1 × 102 CFU was administered. Mice were restrained but not anaesthetised for these procedures (Figure 1(A): Experiment plan of the IP exposure model; Figure 4(A): Experiment plan of the oral exposure model).


Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis.

Poyntz HC, Stylianou E, Griffiths KL, Marsay L, Checkley AM, McShane H - Tuberculosis (Edinb) (2014)

Cellular responses in BCG vaccinated mice that were or were not sensitised with MA 724 IP after BCG Responses were assayed at the 12 month time point; 4 weeks after the last dose of MA 724. Cells from inguinal lymph nodes (LN) and spleens were stimulated with PPD-T. (A) Experiment plan (B and C) IFNγ, TNFα and IL-2 production from CD4+ or CD8+ T cells in the LN, (D) IL-17 production from CD4+ T cells in the LN and spleen, (E) IL-4 production from CD4+ T cells in the LN and spleen, (F) expression of CD25, FoxP3 and CD39 on CD4+ T cells from the LN and spleen, (G) IL-10 production from CD4+ T cells in the LN and spleen. B = BCG vaccinated only, BM = BCG vaccinated mice which received MA 724. Results are expressed as a percentage of the CD4+ or CD8+ T cell population and are stimulation specific; media only control well values are subtracted. Each data point represents one mouse and the median is displayed, n = 5. The Mann–Whitney U test was used to determine statistical significance and is shown where differences were significant. Subcutaneous (Sub Cut.), Intraperitoneal (IP), M. avium (MA), Colony Forming Units (CFU), Day 0 (D0), Regulatory T cells (Tregs).
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fig1: Cellular responses in BCG vaccinated mice that were or were not sensitised with MA 724 IP after BCG Responses were assayed at the 12 month time point; 4 weeks after the last dose of MA 724. Cells from inguinal lymph nodes (LN) and spleens were stimulated with PPD-T. (A) Experiment plan (B and C) IFNγ, TNFα and IL-2 production from CD4+ or CD8+ T cells in the LN, (D) IL-17 production from CD4+ T cells in the LN and spleen, (E) IL-4 production from CD4+ T cells in the LN and spleen, (F) expression of CD25, FoxP3 and CD39 on CD4+ T cells from the LN and spleen, (G) IL-10 production from CD4+ T cells in the LN and spleen. B = BCG vaccinated only, BM = BCG vaccinated mice which received MA 724. Results are expressed as a percentage of the CD4+ or CD8+ T cell population and are stimulation specific; media only control well values are subtracted. Each data point represents one mouse and the median is displayed, n = 5. The Mann–Whitney U test was used to determine statistical significance and is shown where differences were significant. Subcutaneous (Sub Cut.), Intraperitoneal (IP), M. avium (MA), Colony Forming Units (CFU), Day 0 (D0), Regulatory T cells (Tregs).
Mentions: Frozen aliquots of bacteria were thawed and sonicated. Where MA was to be given heat-killed, the aliquots were placed in a water bath at 80 °C for 25 min. Bacteria were then diluted to the required concentration in sterile PBS before administration. 100 μl of BCG in PBS was injected subcutaneously (SC) at the base of the tail using a U-100 29G syringe. 1 × 105 CFU was administered. 100 μl of MA 724 or 2-151 for intraperitoneal injection (IP) was suspended in PBS and administered with a U-100 29G syringe in the right or left side of the peritoneal cavity. In the IP exposure model 1 × 108 CFU of killed MA strain 2-151 or 724 were administered. In the model of oral exposure mice received 100 μl of live MA 104 suspended in PBS via a dosing cannula inserted directly in to the stomach. 1 × 102 CFU was administered. Mice were restrained but not anaesthetised for these procedures (Figure 1(A): Experiment plan of the IP exposure model; Figure 4(A): Experiment plan of the oral exposure model).

Bottom Line: The efficacy of Bacillus Calmette-Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations.CD4+ and CD8+ T cell responses were profiled to define the immunological mechanisms underlying any effect on BCG efficacy.BCG efficacy was reduced by exposure to live MA administered by the oral route; T helper 2 cells were associated with reduced protection.

View Article: PubMed Central - PubMed

Affiliation: The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom. Electronic address: hpoyntz@malaghan.org.nz.

Show MeSH
Related in: MedlinePlus