Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of Prior<i>Mycobacterium bovis</i>BCG Immunization

Palendira, Umaimainthan; Bean, Andrew G. D.; Feng, Carl G.; Britton, Warwick J.

doi:10.1128/iai.70.3.1410-1416.2002

Cited by 51 publications

(48 citation statements)

References 28 publications

(22 reference statements)

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“…Furthermore, it is believe that after mucosal vaccination, Ag-specific memory T cells preferentially home back to the site of vaccination and other mucosal sites (33). Recently, certain integrin molecules have been implicated in mucosal T cell homing (34), and in this regard, ␣ 4 integrin has been associated with higher levels of IFN-␥ ϩ T cells in the lung after mycobacterial challenge (35,36). Whether this is the case in our model remains to be investigated.…”

Section: Discussionmentioning

confidence: 82%

Mechanisms of Mucosal and Parenteral Tuberculosis Vaccinations: Adenoviral-Based Mucosal Immunization Preferentially Elicits Sustained Accumulation of Immune Protective CD4 and CD8 T Cells within the Airway Lumen

Santosuosso

Zhang

McCormick

et al. 2005

The Journal of Immunology

153

225

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The mechanisms underlying better immune protection by mucosal vaccination have remained poorly understood. In our current study we have investigated the mechanisms by which respiratory virus-mediated mucosal vaccination provides remarkably better immune protection against pulmonary tuberculosis than parenteral vaccination. A recombinant adenovirus-based tuberculosis (TB) vaccine expressing Mycobacterium tuberculosis Ag85A (AdAg85A) was administered either intranasally (i.n.) or i.m. to mice, and Ag-specific CD4 and CD8 T cell responses, including frequency, IFN-γ production, and CTL, were examined in the spleen, lung interstitium, and airway lumen. Although i.m. immunization with AdAg85A led to activation of T cells, particularly CD8 T cells, in the spleen and, to a lesser extent, in the lung interstitium, it failed to elicit any T cell response in the airway lumen. In contrast, although i.n. immunization failed to effectively activate T cells in the spleen, it uniquely elicited higher numbers of Ag-specific CD4 and CD8 T cells in the airway lumen that were capable of IFN-γ production and cytolytic activities, as assessed by an intratracheal in vivo CTL assay. These airway luminal T cells of i.n. immunized mice or splenic T cells of i.m. immunized mice, upon transfer locally to the lungs of naive SCID mice, conferred immune protection against M. tuberculosis challenge. Our study has demonstrated that the airway luminal T cell population plays an important role in immune protection against pulmonary TB, thus providing mechanistic insights into the superior immune protection conferred by respiratory mucosal TB vaccination.

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Section: Discussionmentioning

confidence: 82%

Mechanisms of Mucosal and Parenteral Tuberculosis Vaccinations: Adenoviral-Based Mucosal Immunization Preferentially Elicits Sustained Accumulation of Immune Protective CD4 and CD8 T Cells within the Airway Lumen

Santosuosso

Zhang

McCormick

et al. 2005

The Journal of Immunology

153

225

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“…The persistence of these memory cells after the original exposure may allow them to play a significant role in providing long-term cell-mediated immunity to inhaled pathogens. Different approaches to vaccination have been shown to alter the degree to which antigen-specific memory cells are localized to the lung (29). Further assessment of these responses may therefore provide a means to evaluate and optimize vaccination strategies aimed at preventing infection with M. tuberculosis and other respiratory pathogens controlled by cell-mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

Resident Th1-Like Effector Memory Cells in Pulmonary Recall Responses toMycobacterium tuberculosis

Walrath

Zukowski

Krywiak

et al. 2005

Am J Respir Cell Mol Biol

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We recently described a model of Th1 recall responses based on segmental antigen challenge with purified protein derivative of Mycobacterium tuberculosis (PPD). Bronchoscopic instillation of 0.5 tuberculin units of PPD resulted in localized lymphocytic inflammation in PPD-positive subjects only. Recruited lymphocytes were predominantly CD4ϩ and were enriched for cells capable of PPDspecific interferon (IFN)-␥ production. In the current study, we investigated the mechanisms by which this localized recall response is mobilized. Bronchoscopic PPD challenge of skin test-positive subjects resulted in the production of CXCR3 ligands IFN-␥-inducible protein (IP)-10 and monokine induced by IFN-␥ (Mig), but not of CCR5 ligands macrophage inflammatory protein-1␣ and regulatedupon activation, normal T-cell expressed and secreted, whereas skin test-negative subjects produced none of these chemokines. The great majority of individuals infected with Mycobacterium tuberculosis do not develop active disease, but instead develop specific cell-mediated immunity that is manifest clinically by the development of positive skin-test responses to purified protein derivative of M. tuberculosis (PPD) (1). Skin-test responsiveness is associated with relative protection against subsequent infection with M. tuberculosis (2), although the mechanisms by which this protection is mediated remain poorly understood. We previously sought to establish a model of M. tuberculosis-specific recall responses in the human lung to provide a means to investigate the local responses of immune individuals upon re-exposure to the organism. To do so, we adapted the technique of bronchoscopic segmental antigen challenge that had previously been used extensively to characterize the local Th2-mediated immune responses in the lungs of individuals with atopic asthma using challenge with allergens such as ragweed (3-5). We instead used PPD as the challenge antigen, and compared responses of naturally infected skin test-positive subjects with those of healthy PPD-negative control subjects. A baseline bronchoalveolar lavage (BAL) was performed, followed by administration of 0.5 tuberculin units (TU) of PPD (i.e., 1/10th of the standard skintest dose) into the challenged segment and a control instillation of 10 cc of normal saline into a corresponding segment of the contralateral lung. Repeat BAL of control and challenged segments was performed 48 h later.In our initial studies, we demonstrated that bronchoscopic challenge with PPD resulted in a localized inflammatory response in challenged lung segments of PPD-positive subjects only. Compared with BAL of both baseline and control lung segments of these subjects, PPD-challenged segments displayed a 2.7-fold increase in the total BAL cells and an increase in the percentage of BAL lymphocytes from 10% to 19%. PPDchallenged segments of skin test-positive subjects also displayed an increased percentage of CD4ϩ T cells, and were enriched for cells capable of antigen-specific production of interferon (IFN)-␥ in response to ...

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“…Immunization via the i.v. route has been shown to result in the same level of protection against M. tuberculosis challenge as immunization via the s.c. route (44). At 120 days after vaccination, animals were aerosol challenged with 100-200 CFU of M. tuberculosis H37Rv or Beijing/W per lung using an aerosol chamber (Glas-Col) as described (42).…”

Section: Methodsmentioning

confidence: 99%

Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin

Grode

Seiler

Baumann

et al. 2005

Journal of Clinical Investigation

498

428

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The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) was equipped with the membraneperforating listeriolysin (Hly) of Listeria monocytogenes, which was shown to improve protection against Mycobacterium tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG (hly + rBCG) vaccine was shown to protect significantly better against aerosol infection with M. tuberculosis than did the parental BCG strain. The isogenic, urease C-deficient hly + rBCG (∆ureC hly + rBCG) vaccine, providing an intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited still higher vaccine efficacy than parental BCG. ∆ureC hly + rBCG also induced profound protection against a member of the M. tuberculosis Beijing/W genotype family while parental BCG failed to do so consistently. Hly not only promoted antigen translocation into the cytoplasm but also apoptosis of infected macrophages. We concluded that superior vaccine efficacy of ∆ureC hly + rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell-mediated immunity.

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

Abstract: Mycobacterium tuberculosis infects humans through the lung, and immunity to this chronic infection is

Cited by 51 publications

References 28 publications

Mechanisms of Mucosal and Parenteral Tuberculosis Vaccinations: Adenoviral-Based Mucosal Immunization Preferentially Elicits Sustained Accumulation of Immune Protective CD4 and CD8 T Cells within the Airway Lumen

Mechanisms of Mucosal and Parenteral Tuberculosis Vaccinations: Adenoviral-Based Mucosal Immunization Preferentially Elicits Sustained Accumulation of Immune Protective CD4 and CD8 T Cells within the Airway Lumen

Resident Th1-Like Effector Memory Cells in Pulmonary Recall Responses toMycobacterium tuberculosis

Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin

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