Phenotypic maturation of porcine NK- and T-cell subsets

Talker, Stephanie C.; Käser, Tobias; Reutner, Katharina; Sedlak, Corinna; Mair, Kerstin H.; Koinig, Hanna C.; Graage, Robert; Viehmann, Miriam; Klingler, Eva; Ladinig, Andrea; Ritzmann, M.; Saalmüller, Armin; Gerner, Wilhelm

doi:10.1016/j.dci.2013.01.003

Cited by 112 publications

(140 citation statements)

References 54 publications

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“…The overall toolbox for the analysis of pig immune response has greatly increased these last decades, for instance the development of ELISA, ELISPOT (CD4, CD8, and Ab-secreting cells) (79,80) and multiparametric cytometry analysis (79,81,82). These tools can now be combined with the use of SPF (83), inbred (84), and transgenic animals (85)(86)(87) and the complete genome sequence publication (88), to accurately monitor the vaccinal responses of pigs.…”

Section: Discussionmentioning

confidence: 98%

Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

Marquet

Manh

Maisonnasse

et al. 2014

The Journal of Immunology

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Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the human CD1a(pos) DDC. CD163(low) DDC migrate toward CCL21, they activate allogeneic CD8 and CD4 T cells and, like their potential human lung counterpart, they skew CD4 T cells toward a Th17 profile. We thus conclude that swine skin is a relevant model for human skin vaccination.

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Section: Discussionmentioning

confidence: 98%

Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

Marquet

Manh

Maisonnasse

et al. 2014

The Journal of Immunology

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“…Appropriate secondary and isotype controls were included. Where not specified, antibodies were produced in-house from hybridoma cultures, purified and biotinylated or conjugated to fluorochromes as described elsewhere [38]. CD3-eFluor450 was obtained by a custom conjugation (eBioscience).…”

Section: Methodsmentioning

confidence: 99%

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

et al. 2014

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Natural killer (NK) cells are important players in the innate immune response against influenza A virus and the activating receptor NKp46, which binds hemagglutinin on the surface of infected cells, has been assigned a role in this context. As pigs are natural hosts for influenza A viruses and pigs possess both NKp46− and NKp46+ NK cells, they represent a good animal model for studying the role of the NKp46 receptor during influenza. We explored the role of NK cells in piglets experimentally infected with 2009 pandemic H1N1 influenza virus by flow cytometric analyses of cells isolated from blood and lung tissue and by immunostaining of lung tissue sections. The number of NKp46+ NK cells was reduced while NKp46− NK cells remained unaltered in the blood 1–3 days after infection. In the lungs, the intensity of NKp46 expression on NK cells was increased during the first 3 days, and areas where influenza virus nucleoprotein was detected were associated with increased numbers of NKp46+ NK cells when compared to uninfected areas. NKp46+ NK cells in the lung were neither found to be infected with influenza virus nor to be undergoing apoptosis. The binding of porcine NKp46 to influenza virus infected cells was verified in an in vitro assay. These data support the involvement of porcine NKp46+ NK cells in the local immune response against influenza virus.

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“…While a comparable analysis of CD27 expression by porcine CD8 T cells is still to be conducted, a longitudinal study of CD27 expression on porcine CD8 T cells from birth to 6 months of age suggested that early effector cells expressed low levels of CD27, which was absent on late effector or memory cells (40). Thus, we may only speculate at this time that the variable level of CD27 expression on CSFV-specific CD8 T cells reflects a mixture of effector and memory phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Phenotype and Functionality of Porcine CD8 T Cell Responses following Vaccination with Live Attenuated Classical Swine Fever Virus (CSFV) and Virulent CSFV Challenge

Franzoni

Kurkure

Edgar

et al. 2013

Clin. Vaccine Immunol.

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Vaccination with live attenuated classical swine fever virus (CSFV) induces solid protection after only 5 days, which has been associated with virus-specific T cell gamma interferon (IFN-␥) responses. In this study, we employed flow cytometry to characterize T cell responses following vaccination and subsequent challenge infections with virulent CSFV. The CD3 ؉ CD4 ؊ CD8 hi T cell population was the first and major source of CSFV-specific IFN-␥. A proportion of these cells showed evidence for cytotoxicity, as evidenced by CD107a mobilization, and coexpressed tumor necrosis factor alpha (TNF-␣). To assess the durability and recall of these responses, a second experiment was conducted where vaccinated animals were challenged with virulent CSFV after 5 days and again after a further 28 days. While virus-specific CD4 T cell (CD3 ؉ CD4 ؉ CD8␣ ؉ ) responses were detected, the dominant response was again from the CD8 T cell population, with the highest numbers of these cells being detected 14 and 7 days after the primary and secondary challenges, respectively. These CD8 T cells were further characterized as CD44 hi CD62L؊ and expressed variable levels of CD25 and CD27, indicative of a mixed effector and effector memory phenotype. The majority of virus-specific IFN-␥ ؉ CD8 T cells isolated at the peaks of the response after each challenge displayed CD107a on their surface, and subpopulations that coexpressed TNF-␣ and interleukin 2 (IL-2) were identified. While it is hoped that these data will aid the rational design and/or evaluation of next-generation marker CSFV vaccines, the novel flow cytometric panels developed should also be of value in the study of porcine T cell responses to other pathogens/vaccines.

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Phenotypic maturation of porcine NK- and T-cell subsets

Cited by 112 publications

References 54 publications

Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

Assessment of the Phenotype and Functionality of Porcine CD8 T Cell Responses following Vaccination with Live Attenuated Classical Swine Fever Virus (CSFV) and Virulent CSFV Challenge

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