Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of Natural Killer, Cytotoxic T, Natural Killer T and MHC un-restricted cytotoxic T-cells

Denyer, Mick; Wileman, Thomas; Stirling, Catrina; Zuber, Bartek; Takamatsu, H.

doi:10.1016/j.vetimm.2005.10.005

Cited by 108 publications

(108 citation statements)

References 27 publications

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“…In spite of the observed elevation of antigen-specific cytolysis, with the exception of p945 we observed poor titration of target cell killing across several effector-to-target-cell (E:T) ratios (data not shown). A similar lack of titration of cytolysis by bulk PBMCs was previously observed by Denyer and coworkers, who demonstrated that purification of CD6 ϩ cells by positive selection prior to incubating with target cells resulted in titration of cytolytic activity across E:T ratios (11).…”

Section: Mutation Of Fmdv 3c Protease Results In Reduced Capsidsupporting

confidence: 79%

Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

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Pedersen

Toka

et al. 2011

Clin Vaccine Immunol

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Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals, including large and small ruminants and swine. Current vaccine strategies are all directed toward the induction of neutralizing antibody responses. However, the role of cytotoxic T lymphocytes (CTLs) has not received a great deal of attention, in part because of the technical difficulties associated with establishing a reliable assay of cell killing for this highly cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation and effectively increasing the class I major histocompatibility complex (MHC)/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell-targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8؉ CTL killing of MHC-matched target cells in an antigen-specific manner. Further, we confirm these results by MHC tetramer staining. This work presents the first demonstration of FMDV-specific CTL killing and confirmation by MHC tetramer staining in response to vaccination against FMDV.

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Section: Mutation Of Fmdv 3c Protease Results In Reduced Capsidsupporting

confidence: 79%

Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

Patch

Pedersen

Toka

et al. 2011

Clin Vaccine Immunol

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“…Taken together, these characteristics suggest that this trait in particular would be a strong candidate for selective breeding of pigs for enhanced performance under commercial conditions. CD11R1 1 mononuclear cells in pigs express markers and function consistent with NK activity Denyer et al, 2006). In addition, we have described a novel CD11R1 1 population that does not express CD8a, which is larger and more granular than the CD11R1 1 cells positive for CD8a (Clapperton et al, 2005a).…”

Section: Discussionmentioning

confidence: 60%

Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance

Clapperton

Glass

Bishop

2008

Animal

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Indicator traits used to select pigs for increased resistance to infection or improved health must be heritable and, preferably, be associated with improved performance. We estimated the heritability of a range of immune traits and their genetic and phenotypic correlations with growth performance. We measured immune traits on 589 pigs and performance on 1941 pigs from six farms, three of which were classified as 'high health status' (i.e. specific pathogen-free) and three were of lower health status. All pigs were apparently healthy. Immune traits were total white blood cells (WBC), and peripheral blood mononuclear leucocyte (PBML) subsets positive for CD4, CD8a, gamma delta (gd) T cell receptor, CD11R1 (natural killer cell marker), B cell and monocyte markers at the start and the end of standard growth performance tests. At both time points, all immune traits were moderately to highly heritable except for CD8a 1 cells. At end of test, heritability estimates (h 2 ) (6s.e.) were 0.18 (60.11) for total WBC count. For PBML subset proportions, the heritabilities were 0.52 (60.14) for gd TCR 1 cells, 0.62 (60.14) for CD4 1 cells, 0.44 (60.14) for CD11R1 1 cells, 0.58 (60.14) for B cells and 0.59 (60.14) for monocytes. Farm health status affected the heritabilities for WBC, being substantially higher on lower health status farms, but did not have consistent effects on heritabilities for the PBML subsets. There were significant negative genetic correlations between numbers and proportions of various PBML subsets and performance, at both start and end of test. In particular, the proportion of PBML cells that were CD11R1 1 cells, at end of test, was strongly correlated with daily gain (r g 5 20.72; P , 0.01). There were also weaker but significant negative phenotypic correlations between PBML subsets measured at end of test and performance, for gd 1 T cells, CD8a 1 , CD11R1 1 cells, B cells or monocytes. Phenotypic correlations with daily gain were generally lower at the start of test than at the end of test. These results show that most of the major pig PBML subsets are heritable, and that systemic levels of several of these PBML subsets are genetically negatively correlated with performance. This approach provides a basis for using immune trait markers when selecting boars that can produce higher-performing progeny.

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“…The porcine CD4 + CD8 + population contains memory T helper cells that recognize antigens in an MHC class II-restricted manner [33]. The CD4 + CD8 + are multifunctional, as they express perforin and mediate antigen-specific cytolytic activity against virus-infected target cells [34,35]. It is not clear why the CD4 + CD8 + CD25 EI responses of animals vaccinated with NS1 126 TX98 remained low prior to challenge.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs

Kappes

Sandbulte

Platt

et al. 2012

Vaccine

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The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad crossprotection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1Δ126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1Δ126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1Δ126 TX98 infected pigs were minimal. However, intracellular IFN-γ data indicate that the attenuated virus induced virus-specific CD4 + CD8 -, CD4 + CD8 + , CD4 -CD8 + , and γδ T cells within 28 days. The IFN-γ response appeared to contract, as responses were reduced at later time points prior to challenge. CD4 + CD8 + cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1Δ126 TX98 was associated with significantly lower levels of Th1-associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1Δ SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains. The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1 126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1 126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1 126 TX98 infected pigs were minimal. However, intracellular IFN-␥ data indicate that the attenuated virus induced virus-specific CD4 + CD8 -, CD4 + CD8 + , CD4 -CD8 + , and ␥␦ T cells within 28 days. The IFN-␥ response appeared to contract, as responses were reduced at later time points prior to challenge. CD4 + CD8 + cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to virus restimulation. Pigs previously infected with wild type TX98 were protected from replicatio...

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Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of Natural Killer, Cytotoxic T, Natural Killer T and MHC un-restricted cytotoxic T-cells

Cited by 108 publications

References 27 publications

Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance

Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs

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