Both<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mrow><mml:mtext>CD4</mml:mtext></mml:mrow><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math>and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mrow><mml:mtext>CD8</mml:mtext></mml:mrow><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math>Lymphocytes Participate in the IFN-γ Response to Filamentous Hemagglutinin from<i>Bordetella pertussis</i>in Infants, Children, and Adults

Dirix, Violette; Verscheure, Virginie; Vermeulen, Françoise; Schutter, Iris De; Goetghebuer, Tessa; Locht, Camille; Mascart, Françoise

doi:10.1155/2012/795958

Cited by 24 publications

(18 citation statements)

References 50 publications

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“…Our results, showing a clear proliferation of CD4 ϩ and CD8 ϩ T cells of aP-primed children upon pertussis stimulation, are in agreement with studies that showed that CD4 ϩ and CD8 ϩ T cells are involved in the immune response against pertussis (13,21,23). Moreover, the observations that pertussis-specific T CM were more prevalent in CD4 ϩ than in CD8 ϩ T cells and that the relative proportions of T CM and T EM do not change after a booster immunization are in line with other studies on memory T-cell subsets (16,24).…”

Section: Discussionsupporting

confidence: 92%

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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dWhooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4؉ and CD8 ؉ T-cell fractions (CFSE dim ) were higher in aP-than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4؉ effector memory cells (CD45RA ؊ CCR7 ؊ ) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP-and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4 ؉ and CD8 ؉ effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

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Section: Discussionsupporting

confidence: 92%

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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“…There are, however, no reports yet on the role of Tc17 during B. pertussis infection. Although CD8 + T cells were found to be dispensable for resolving B. pertussis infection in the mouse model [22], [23], in humans IFN-γ producing CD8 + T cell responses were detected in a cohort of B. pertussis -infected infants and young adults, as well as in vaccinated children [24]. It remains, hence, to be determined whether these cells are induced by the adjuvant activity of B. pertussis virulence factors, or whether CD8 + T cells actively participate in host defense against B. pertussis .…”

Section: Discussionmentioning

confidence: 99%

Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells

et al. 2014

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Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4+ and CD8+ T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4+CD25+Foxp3+ T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8+ T cell proliferation and limited the induction of IFN-γ producing CD8+ T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.

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“…In terms of the breadth of the responses induced by natural infection versus the different vaccine constructs, epitope data were defined from a relatively small number of B. pertussis antigens (6 of >3400). The majority of epitopes were defined for PT, and far fewer were reported for antigens incorporated within currently licensed aP vaccines, and also associated with vaccine-induced immunity and in immunity to natural infection [11,49–51]. Thus a meaningful assessment of how the epitope breadth elicited by natural infection versus aP and wP vaccination could not be undertaken.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Numerous studies published to date have demonstrated a role for T cells/cell-mediated immunity following immunization and natural infection [11,49,50,60–62]. Despite this, very little of the T cell epitope data were characterized phenotypically.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Similarly, while the wP vaccine has been associated with a Th1/Th17 type response, the aP formulations tend to induce Th2 cytokines [50,65]. Thus far there is little or no characterization of CD8 + T cell epitopes, despite some evidence of their role in natural infection and following immunization [49,61]. Lastly, MHC restriction data was limited.…”

Section: Discussion/conclusionmentioning

confidence: 99%

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Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy

Vaughan¹,

Seymour²,

Peters³

et al. 2014

Human Immunology

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The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. The Immune Epitope Database (IEDB) is a repository of immune epitope data from the published literature and includes T cell and antibody epitopes for human pathogens. The IEDB conducted a review of the epitope literature, which revealed 300 Bordetella pertussis-related epitopes from 39 references. Epitope data are currently available for six virulence factors of B. pertussis: pertussis toxin, pertactin, fimbrial 2, fimbrial 3, adenylate cyclase and filamentous hemagglutinin. The majority of epitopes were defined for antibody reactivity; fewer T cell determinants were reported. Analysis of available protective correlates data revealed a number of candidate epitopes; however few are defined in humans and few have been shown to be protective. Moreover, there are a limited number of studies defining epitopes from natural infection versus whole cell or acellular/subunit vaccines. The relationship between epitope location and structural features, as well as antigenic drift (SNP analysis) was also investigated. We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level.

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BothCD4+andCD8+Lymphocytes Participate in the IFN-γ Response to Filamentous Hemagglutinin fromBordetella pertussisin Infants, Children, and Adults

Cited by 24 publications

References 50 publications

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells

Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy

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