CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis

Lee, Lian Ni; Ronan, Edward O.; Lara, Catherine de; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; Tchilian, Elma; Beverley, Peter C. L.

doi:10.1128/iai.01133-10

Cited by 54 publications

(58 citation statements)

References 55 publications

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“…On the other hand, CD8 + T RM cells expressed significantly higher levels of gamma interferon (IFN-γ) ( Ifng ), tumor necrosis factor alpha (TNF-α) ( Tnfa ), and Cxcr6 (Fig. 5B) (29) and statistically insignificantly higher levels of perforin ( Prf1 ) and granzyme B ( Gzmb ) than their CD8 + T EM counterparts (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

Perdomo

Zedler

Kühl

et al. 2016

mBio

205

228

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Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies.

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Section: Resultsmentioning

confidence: 99%

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

Perdomo

Zedler

Kühl

et al. 2016

mBio

205

228

View full text Add to dashboard Cite

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“…In our microarray studies with CD4 cells purified from Pneumocystis -infected lungs, Cxcr6 was the most significantly upregulated chemotactic factor, and Q-PCR studies confirmed upregulation of both Cxcr6 and its sole ligand, Cxcl16, in wild-type mice. Cxcr6 has been reported to be a marker of protective antigen-specific T cells in the lungs of a mouse model of tuberculosis [34]. Intriguingly, polymorphisms in the Cxcr6 gene in African Americans have been associated with increased mortality in AIDS-related PCP [35].…”

Section: Discussionmentioning

confidence: 99%

Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice

Bishop

Lionakis

Sassi

et al. 2015

Microbes and Infection

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We examined gene expression levels of multiple chemokines and chemokine receptors during Pneumocystis murina infection in wild-type and immunosuppressed mice, using microarrays and qPCR. In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, Cxcr6, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75 to 150. Concomitant increases were seen in Ccr2 ,Cxcr3, and Cxcr6, but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2, Cxcr3, and Cxcr6 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.

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“…In this regard CD8 T-cells primed in the lung draining lymph node were enriched for CCR5 and CXCR3 expression [27]. Furthermore, others have demonstrated that following intranasal vaccination with AdHu5Ag85A, antigen-specific CD8 T-cells localised to the lung expressed high levels of CXCR6 [28]. In addition, we have found CCR1, CCR6, CCR8, CD103 and VLA-1 to be upregulated on activated T-cells by respiratory mucosal, but not by intramuscular, immunisation (unpublished data), suggesting the involvement of multiple molecules in T-cell homing into the lung interstitium and airway.…”

Section: Effect Of Local Pro-inflammatory Signals On the Distributionmentioning

confidence: 92%

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

et al. 2015

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Despite the use of bacille Calmette-Guérin (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. @ERSpublications Immunisation route determines TB vaccine efficacy based on whether T-cells can enter restricted lung mucosal sites http://ow.ly/M0shT

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CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis

Cited by 54 publications

References 55 publications

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

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