The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Zhou Xing - One of the best experts on this subject based on the ideXlab platform.
-
Role of B Cells in Mucosal Vaccine–Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis
Journal of immunology (Baltimore Md. : 1950), 2015Co-Authors: Amandeep Khera, Sam Afkhami, Rocky Lai, Mangalakumari Jeyanathan, Anna Zganiacz, Talveer S. Mandur, Joni Hammill, Daniela Damjanovic, Zhou XingAbstract:Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and Lung Interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and Lung Interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.
-
Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted Lung mucosal compartments
European respiratory review : an official journal of the European Respiratory Society, 2015Co-Authors: Rocky Lai, Sam Afkhami, Mangalakumari Jeyanathan, Siamak Haddadi, Zhou XingAbstract:Despite the use of bacille Calmette-Guerin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the Lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the Lung Interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the Lung Interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the Lung Interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines.
-
Airway luminal T cells: a newcomer on the stage of TB vaccination strategies.
Trends in immunology, 2010Co-Authors: Mangalakumari Jeyanathan, Armando Heriazon, Zhou XingAbstract:Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the Lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in the Lung Interstitium and spleen before Mycobacterium tuberculosis exposure and protection. In contrast, respiratory mucosal immunization leads to distribution of T cells not only in the Lung Interstitium and spleen, but also in the airway lumen, and the presence of these cells correlates well with protection. Furthermore, airway luminal recruitment of parenteral vaccine-induced T cells in peripheral tissues prior to M. tuberculosis challenge restores protection. We propose that understanding the biology of airway luminal T cells holds important implications for developing effective TB vaccination strategies.
-
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
Journal of immunology (Baltimore Md. : 1950), 2005Co-Authors: Michael Santosuosso, Xizhong Zhang, Sarah Mccormick, Jun Wang, Mary Hitt, Zhou XingAbstract: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.
Mangalakumari Jeyanathan - One of the best experts on this subject based on the ideXlab platform.
-
Role of B Cells in Mucosal Vaccine–Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis
Journal of immunology (Baltimore Md. : 1950), 2015Co-Authors: Amandeep Khera, Sam Afkhami, Rocky Lai, Mangalakumari Jeyanathan, Anna Zganiacz, Talveer S. Mandur, Joni Hammill, Daniela Damjanovic, Zhou XingAbstract:Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and Lung Interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and Lung Interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.
-
Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted Lung mucosal compartments
European respiratory review : an official journal of the European Respiratory Society, 2015Co-Authors: Rocky Lai, Sam Afkhami, Mangalakumari Jeyanathan, Siamak Haddadi, Zhou XingAbstract:Despite the use of bacille Calmette-Guerin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the Lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the Lung Interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the Lung Interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the Lung Interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines.
-
Airway luminal T cells: a newcomer on the stage of TB vaccination strategies.
Trends in immunology, 2010Co-Authors: Mangalakumari Jeyanathan, Armando Heriazon, Zhou XingAbstract:Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the Lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in the Lung Interstitium and spleen before Mycobacterium tuberculosis exposure and protection. In contrast, respiratory mucosal immunization leads to distribution of T cells not only in the Lung Interstitium and spleen, but also in the airway lumen, and the presence of these cells correlates well with protection. Furthermore, airway luminal recruitment of parenteral vaccine-induced T cells in peripheral tissues prior to M. tuberculosis challenge restores protection. We propose that understanding the biology of airway luminal T cells holds important implications for developing effective TB vaccination strategies.
Reinhard Pabst - One of the best experts on this subject based on the ideXlab platform.
-
Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP-2 in rats is age dependent.
Immunology letters, 2007Co-Authors: Anke Lührmann, Karsten Grote, Michael Stephan, Thomas Tschernig, Reinhard PabstAbstract:Recent studies indicate that the pulmonary immune response in humans and experimental animals is different in newborn, adult and elderly age groups. The aim of this study was to investigate the influence of age on the leukocyte composition in different Lung compartments and peripheral blood of weaned and adult rats. A mycoplasma-like inflammatory response was mimicked by intratracheal application of the synthetic macrophage-activating lipopeptide-2 (MALP-2) which activates macrophages and other cells via the Toll-like receptor (TLR) 2 and 6. TLR 2 and 6 mRNA expressions were investigated by semiquantitative RT-PCR in cells of the bronchoalveolar lavage (BAL) and Lung Interstitium. Weaned Lewis rats (3-4 weeks old) and adults (12-14 months old) were treated with vehicle control or MALP-2. Cytokines and cell infiltration were measured in the BAL and Lung Interstitium. In control rats, no differences in TLR 2 and 6 mRNA expression level were found between the age groups. After MALP-2 treatment, the maximum of MCP-1 concentration in the BAL fluid was reached in weaned rats after 4h and in adults after 2h. The TNF-alpha maximum was measured after 2h in both age groups. Three days after MALP-2 the numbers of different leukocyte subsets were significantly increased in the BAL of both groups. In contrast, in the Lung Interstitium MALP-2 induced a leukocyte increase in adult rats but not in weaned rats. In conclusion, data on pulmonary immune responses from one age group and one Lung compartment should not be generalized or extrapolated to other groups.
-
Perivascular capillaries in the Lung: an important but neglected vascular bed in immune reactions?
The Journal of allergy and clinical immunology, 2002Co-Authors: Reinhard Pabst, Thomas TschernigAbstract:In allergic and inflammatory immune reactions of the respiratory tract, leukocytes migrate into the different compartments of the Lung. The air space can easily be sampled by means of bronchoalveolar lavage. However, the subset composition in the bronchial wall or the Lung Interstitium often differs considerably from that of the bronchoalveolar lavage fluid. A further compartment involved in very heterogeneous immune reactions in the Lung has thus far not been mentioned: the periarterial space. In numerous experiments in different species with virus, bacteria, fungi, or allergens, there was not only a leukocyte infiltration of the bronchial lamina propria but also infiltration around branches of the pulmonary artery. This thus far neglected compartment consists of a different type of capillary. Thus it is important not to overlook this area in studies on allergic or inflammatory immune reactions of the Lung.
-
Increased expression of activation markers and adhesion molecules on Lung T-cells compared with blood in the normal rat.
The European respiratory journal, 1999Co-Authors: Thomas Tschernig, Frank G. Fliegert, J Westermann, Reinhard PabstAbstract:Lymphocytes play an important role in many Lung diseases and are routinely accessible by bronchoalveolar lavage (BAL). Lymphocytes from the BAL (BAL pool) have a different subset composition to those from peripheral blood, consisting mainly of activated T-cells. The aim of this study was to examine whether preferential migration of activated T-cells to the bronchoalveolar space or factors of the specific microenvironment mediate this phenomenon. The expression of adhesion molecules and cellular activation markers (intercellular adhesion molecule-1, leukocyte function-associated antigen-1, CD2, CD44, interleukin-2 receptor and L-selectin) was studied on T- and B-cells not only in the BAL and peripheral blood (blood pool), but also in the compartments in between, such as the Lung vascular perfusate (marginal pool) and the Lung Interstitium (interstitial pool), with the experiments being performed simultaneously in the same animals. Low levels of adhesion molecule expression were observed on T-cells in the blood and marginal pool, medium levels in the Lung Interstitium and the highest levels in the BAL. "Memory" (CD45R(low)) and "naive" (CD45R(high)) T-cells in the Lung compartments showed a higher expression of adhesion molecules compared with blood. However, the predominating CD45R(low) T-cells showed a significantly higher expression than the CD45R(high) cells, indicating that CD4+ CD45R(high) T-cells had changed their phenotype to CD45R(low). In conclusion, a high level of expression of leukocyte function associated antigen-1 and intracellular adhesion molecule-1 on the bronchoalveolar lavage and interstitial T-cells is more likely to be the result of local, Lung-specific induction than a prerequisite for migration into the bronchoalveolar space.
-
Comparison of lymphocyte subsets, monocytes, and NK cells in three different Lung compartments and peripheral blood in the rat.
Experimental lung research, 1996Co-Authors: Frank G. Fliegert, Thomas Tschernig, Reinhard PabstAbstract:Investigations on leukocyte populations in the Lung have shown that lymphocytes are found in different anatomical compartments. Lymphocytes can be seen to a different extent in the Lung Interstitium, the epithelium and lamina propria of the bronchi, the bronchoalveolar space, and the marginal Lung vascular bed. Previous studies focused on one compartment only, or a mixture of leukocytes from Lung homogenates were prepared. This study compared cellular yields from the Lung parenchyma, the bronchoalveolar space, and the perfusate of the Lung vasculature of healthy male Lewis rats. All compartments were investigated in the same animal, and seven different lymphocyte subsets, monocytes, and natural killer (NK) cells were analyzed using flow cytometry. It was found that the perfusate contained a high proportion of CD4+ lymphocytes compared to the Lung Interstitium. A very high proportion of CD4+ lymphocytes in the bronchoalveolar lavage (BAL) expressed markers for “memory” T cells. Compared to the blood, the p...
Thomas Tschernig - One of the best experts on this subject based on the ideXlab platform.
-
Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP-2 in rats is age dependent.
Immunology letters, 2007Co-Authors: Anke Lührmann, Karsten Grote, Michael Stephan, Thomas Tschernig, Reinhard PabstAbstract:Recent studies indicate that the pulmonary immune response in humans and experimental animals is different in newborn, adult and elderly age groups. The aim of this study was to investigate the influence of age on the leukocyte composition in different Lung compartments and peripheral blood of weaned and adult rats. A mycoplasma-like inflammatory response was mimicked by intratracheal application of the synthetic macrophage-activating lipopeptide-2 (MALP-2) which activates macrophages and other cells via the Toll-like receptor (TLR) 2 and 6. TLR 2 and 6 mRNA expressions were investigated by semiquantitative RT-PCR in cells of the bronchoalveolar lavage (BAL) and Lung Interstitium. Weaned Lewis rats (3-4 weeks old) and adults (12-14 months old) were treated with vehicle control or MALP-2. Cytokines and cell infiltration were measured in the BAL and Lung Interstitium. In control rats, no differences in TLR 2 and 6 mRNA expression level were found between the age groups. After MALP-2 treatment, the maximum of MCP-1 concentration in the BAL fluid was reached in weaned rats after 4h and in adults after 2h. The TNF-alpha maximum was measured after 2h in both age groups. Three days after MALP-2 the numbers of different leukocyte subsets were significantly increased in the BAL of both groups. In contrast, in the Lung Interstitium MALP-2 induced a leukocyte increase in adult rats but not in weaned rats. In conclusion, data on pulmonary immune responses from one age group and one Lung compartment should not be generalized or extrapolated to other groups.
-
Perivascular capillaries in the Lung: an important but neglected vascular bed in immune reactions?
The Journal of allergy and clinical immunology, 2002Co-Authors: Reinhard Pabst, Thomas TschernigAbstract:In allergic and inflammatory immune reactions of the respiratory tract, leukocytes migrate into the different compartments of the Lung. The air space can easily be sampled by means of bronchoalveolar lavage. However, the subset composition in the bronchial wall or the Lung Interstitium often differs considerably from that of the bronchoalveolar lavage fluid. A further compartment involved in very heterogeneous immune reactions in the Lung has thus far not been mentioned: the periarterial space. In numerous experiments in different species with virus, bacteria, fungi, or allergens, there was not only a leukocyte infiltration of the bronchial lamina propria but also infiltration around branches of the pulmonary artery. This thus far neglected compartment consists of a different type of capillary. Thus it is important not to overlook this area in studies on allergic or inflammatory immune reactions of the Lung.
-
Increased expression of activation markers and adhesion molecules on Lung T-cells compared with blood in the normal rat.
The European respiratory journal, 1999Co-Authors: Thomas Tschernig, Frank G. Fliegert, J Westermann, Reinhard PabstAbstract:Lymphocytes play an important role in many Lung diseases and are routinely accessible by bronchoalveolar lavage (BAL). Lymphocytes from the BAL (BAL pool) have a different subset composition to those from peripheral blood, consisting mainly of activated T-cells. The aim of this study was to examine whether preferential migration of activated T-cells to the bronchoalveolar space or factors of the specific microenvironment mediate this phenomenon. The expression of adhesion molecules and cellular activation markers (intercellular adhesion molecule-1, leukocyte function-associated antigen-1, CD2, CD44, interleukin-2 receptor and L-selectin) was studied on T- and B-cells not only in the BAL and peripheral blood (blood pool), but also in the compartments in between, such as the Lung vascular perfusate (marginal pool) and the Lung Interstitium (interstitial pool), with the experiments being performed simultaneously in the same animals. Low levels of adhesion molecule expression were observed on T-cells in the blood and marginal pool, medium levels in the Lung Interstitium and the highest levels in the BAL. "Memory" (CD45R(low)) and "naive" (CD45R(high)) T-cells in the Lung compartments showed a higher expression of adhesion molecules compared with blood. However, the predominating CD45R(low) T-cells showed a significantly higher expression than the CD45R(high) cells, indicating that CD4+ CD45R(high) T-cells had changed their phenotype to CD45R(low). In conclusion, a high level of expression of leukocyte function associated antigen-1 and intracellular adhesion molecule-1 on the bronchoalveolar lavage and interstitial T-cells is more likely to be the result of local, Lung-specific induction than a prerequisite for migration into the bronchoalveolar space.
-
Comparison of lymphocyte subsets, monocytes, and NK cells in three different Lung compartments and peripheral blood in the rat.
Experimental lung research, 1996Co-Authors: Frank G. Fliegert, Thomas Tschernig, Reinhard PabstAbstract:Investigations on leukocyte populations in the Lung have shown that lymphocytes are found in different anatomical compartments. Lymphocytes can be seen to a different extent in the Lung Interstitium, the epithelium and lamina propria of the bronchi, the bronchoalveolar space, and the marginal Lung vascular bed. Previous studies focused on one compartment only, or a mixture of leukocytes from Lung homogenates were prepared. This study compared cellular yields from the Lung parenchyma, the bronchoalveolar space, and the perfusate of the Lung vasculature of healthy male Lewis rats. All compartments were investigated in the same animal, and seven different lymphocyte subsets, monocytes, and natural killer (NK) cells were analyzed using flow cytometry. It was found that the perfusate contained a high proportion of CD4+ lymphocytes compared to the Lung Interstitium. A very high proportion of CD4+ lymphocytes in the bronchoalveolar lavage (BAL) expressed markers for “memory” T cells. Compared to the blood, the p...
Pavlo Gilchuk - One of the best experts on this subject based on the ideXlab platform.
-
a distinct Lung Interstitium resident memory cd8 t cell subset confers enhanced protection to lower respiratory tract infection
Cell Reports, 2016Co-Authors: Pavlo Gilchuk, Timothy M Hill, Clifford S Guy, Sean R Mcmaster, Kelli L Boyd, Whitney Rabacal, Yu Shyr, Jacob E Kohlmeier, Eric SebzdaAbstract:Summary The nature and anatomic location of the protective memory CD8 + T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8 + T cells and their role in lower airway infections. Memory CD8 + T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8 + T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3 LO resident memory CD8 + T (Trm) cell population that preferentially localizes to the pulmonary Interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8 + T cells into the Lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce Lung interstitial Trm cells may confer better protection against respiratory pathogens.
