Immune Responses in Mice After Gastric and Subcutaneous Immunization with BCG

Ibsen, Margrethe W; Bakken, Vidar; Jönsson, Roland; Hordnes, Knut

doi:10.1046/j.1365-3083.1997.d01-116.x

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…In our initial studies we wished to establish the character of the immune response induced by BCG via the intravesical route. Previous studies have shown that immunization by different routes generate diverse effector responses [27,40]. Moreover, it is known that mycobacteria can induce both Th1 and Th2 responses[16,41].…”

Section: Discussionmentioning

confidence: 99%

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity

Nadler

Luo

Zhao

et al. 2003

Clinical and Experimental Immunology

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SUMMARYIntravesical BCG therapy is effective in the treatment of superficial bladder cancer. Both clinical and experimental results suggest a role for cytokines and delayed-type hypersensitivity (DTH) in BCGinduced antitumour immunity. We characterized the modulatory effects of BCG on bladder cytokine expression and determined the relationship between DTH and BCG antitumour activity. The bladders of mice were instilled with BCG through a catheter. Bladder tissue RNA and urine were collected for evaluation of cytokine expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ELISA. IFN-g and TNF-a , the two major cytokines associated with DTH, were efficiently induced by BCG. IL10, an important down-regulator of DTH, was also induced by BCG. Constitutive levels of IL4 and IL5 were observed, but neither IL4 nor IL5 were modulated by BCG. Similar results were observed in the kinetic analysis of urinary cytokines in patients after intravesical BCG therapy. Production of Th1 (T helper type 1) cytokines (IFN-g , IL2 and IL12) preceded that of the Th2 (T helper type 2) cytokine IL10. A tendency toward higher ratios of IFN-g versus IL10 for BCG responders also was observed. In animal studies the absence of IL10 abrogated either by antibody inhibition or the use of genetically modified, IL10 deficient (IL10 -/-) mice resulted in enhanced DTH responses. Under conditions of enhanced DTH, a significant enhancement in antitumour activity was observed. These data demonstrate that DTH and its associated mononuclear infiltration and cytokine production are important to the antitumour activity of intravesical BCG therapy, and suggest that effects to diminish IL10 production may have therapeutic value.

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Section: Discussionmentioning

confidence: 99%

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity

Nadler

Luo

Zhao

et al. 2003

Clinical and Experimental Immunology

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“…A substantial body of literature exists documenting immune responses to systemic challenge with mycobacteria in murine models [6–8]. However, it has been demonstrated that immune responses to systemic and lung infections with mycobacteria are substantially different.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of changes in lymphocyte sub-populations in mouse lungs after intrapulmonary infection withM. bovis(Bacillus Calmette-Guerin) and identity of cells responsible for IFNγ responses

Saxena

Weissman

Saxena

et al. 2002

Clinical and Experimental Immunology

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) cells. As the BCG lung infection peaked, the total number of CD3 + T cells in the lungs increased threefold at 5-6 weeks post-infection. There was a marked increase (sixfold) in the number of T cells secreting IFNg 5-6 weeks post-infection. Some increase was also noted in the NKT cells making IFNg, but the numbers of NK cells making IFNg in BCG-infected lungs remained unaltered. Our results suggest that whereas NK and NKT cells contribute to baseline IFNg secretion in control lungs, expansion in the IFNg-producing T-cell population was essentially responsible for the augmented response seen in lungs of BCG-infected mice.

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Murine model of BCG lung infection: Dynamics of lymphocyte subpopulations in lung interstitium and tracheal lymph nodes

et al. 2002

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C57Bl/6 female mice were infected with an intrapulmonary dose of 2.5 x 10(4) BCG (Mycobacterium bovis Bacillus Calmette-Guerin). Lymphocyte populations in lung interstitium and lung-associated tracheal lymph nodes (LN) were examined at 1, 2, 4, 5, 6, 8 and 12 weeks after infection. BCG load in lungs peaked between 4-6 weeks post-infection and declined to very low levels by the 12th week of infection. Lung leukocytes were obtained over the course of infection by enzyme digestion of lung tissue followed by centrifugation over Percoll discontinuous density gradients. By 4 to 6 weeks after infection, numbers of lung leukocytes had more than doubled but the proportions of lymphocytes (about 70%), macrophages (about 18%) and granulocytes (about 12%) remained essentially unaltered. Flow cytometric studies indicated: (i) the total number of CD3+ T cells in lungs increased by 3-fold relative to uninfected controls at 5 to 6 weeks post-infection, but the relative proportions of CD4 and CD8 cells within the T cell compartment remained unaltered; (ii) relative proportion of NK cells in lungs declined by 30% but the total number of NK cells (NK1.1+) per lung increased by about 50%, 5-6 weeks post infection; (iii) tracheal LN underwent marked increase in size and cell recoveries (6-10-fold increase) beginning 4 weeks after infection. While both T and B cells contributed to the increase in cell recoveries from infected tracheal LNs, the T/B ratio declined significantly but CD4/CD8 ratio remained unaltered. In control mice, IFNgamma producing non-T cells outnumbered T cells producing IFNgamma. However, as the adaptive response to infection evolves, marked increase occur in the number of IFNgamma producing T cells, but not NK cells in the lungs. Thus, T cells are the primary cell type responsible for the adaptive IFNgamma response to pulmonary BCG infection. Few T cells in tracheal LN of BCG infected mice produce IFNgamma, suggesting that maturational changes associated with migration to the lungs or residence in the lungs enhance the capability of some T cells to produce this cytokine.

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Immune Responses in Mice After Gastric and Subcutaneous Immunization with BCG

Cited by 5 publications

References 26 publications

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity

Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumour activity

Kinetics of changes in lymphocyte sub-populations in mouse lungs after intrapulmonary infection withM. bovis(Bacillus Calmette-Guerin) and identity of cells responsible for IFNγ responses

Murine model of BCG lung infection: Dynamics of lymphocyte subpopulations in lung interstitium and tracheal lymph nodes

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