Cytolytic Function for Pseudorabies Virus-Stimulated Porcine CD4<sup>+</sup>CD8<sup>dull+</sup>Lymphocytes

Bruin, M.G. de; Rooij, E.M. van; Visser, Y.E. de; Bianchi, A.T.J.

doi:10.1089/vim.2000.13.511

Cited by 34 publications

(28 citation statements)

References 37 publications

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“…Consistent with that, an increased frequency of activated CD4 ϩ T cells associated with enhanced generation of the SwIV-specific mucosal IgA and an increased frequency of activated CD8 ϩ T cells in pig lungs were detected. Activated CD4 ϩ CD8 ϩ T cells in pigs possess T-helper, cytolytic, and memory properties, important for the viral clearance (12). Interestingly, in SwIV-infected BAL fluid, TBLN, and tonsils, significantly higher frequencies of CD4 ϩ CD8 ϩ T cells were detected.…”

Section: Discussionmentioning

confidence: 97%

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

Khatri¹,

Dwivedi²,

Krakowka

et al. 2010

J Virol

127

141

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Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-␥ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, ␥␦ T cells, dendritic cells, activated T cells, and CD4؉ and CD8 ؉ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

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Section: Discussionmentioning

confidence: 97%

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

Khatri¹,

Dwivedi²,

Krakowka

et al. 2010

J Virol

127

141

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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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“…Summerfield et al [23] demonstrated that CD4+CD8+ cells can function as memory T-helper cells which proliferate upon stimulation with recall antigen. The CD4+CD8+ T cells were found to be associated with protection in pigs vaccinated against PRV [24]. The study of the cellular immune response to virus or vaccines in the natural host is of the utmost importance for understanding the interaction between the pathogen and the swine immune system [25].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study for T lymphocyte subpopulations in swine

Lü

Luo

et al. 2012

BMC Genomics

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BackgroundLymphocytes act as a major component of the adaptive immune system, taking very crucial responsibility for immunity. Differences in proportions of T-cell subpopulations in peripheral blood among individuals under same conditions provide evidence of genetic control on these traits, but little is known about the genetic mechanism of them, especially in swine. Identification of the genetic control on these variants may help the genetic improvement of immune capacity through selection.ResultsTo identify genomic regions responsible for these immune traits in swine, a genome-wide association study was conducted. A total of 675 pigs of three breeds were involved in the study. At 21 days of age, all individuals were vaccinated with modified live classical swine fever vaccine. Blood samples were collected when the piglets were 20 and 35 days of age, respectively. Seven traits, including the proportions of CD4+, CD8+, CD4+CD8+, CD4+CD8−, CD4−CD8+, CD4−CD8− and the ratio of CD4+ to CD8+ T cells were measured at the two ages. All the samples were genotyped for 62,163 single nucleotide polymorphisms (SNP) using the Illumina porcineSNP60k BeadChip. 40833 SNPs were selected after quality control for association tests between SNPs and each immune trait considered based on a single-locus regression model. To tackle the issue of multiple testing in GWAS, 10,000 permutations were performed to determine the chromosome-wise and genome-wise significance levels of association tests. In total, 61 SNPs with chromosome-wise significance level and 3 SNPs with genome-wise significance level were identified. 27 significant SNPs were located within the immune-related QTL regions reported in previous studies. Furthermore, several significant SNPs fell into the regions harboring known immunity-related genes, 14 of them fell into the regions which harbor some known T cell-related genes.ConclusionsOur study demonstrated that genome-wide association studies would be a feasible way for revealing the potential genetics variants affecting T-cell subpopulations. Results herein lay a preliminary foundation for further identifying the causal mutations underlying swine immune capacity in follow-up studies.

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Cytolytic Function for Pseudorabies Virus-Stimulated Porcine CD4⁺CD8^dull+Lymphocytes

Cited by 34 publications

References 37 publications

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

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

Genome-wide association study for T lymphocyte subpopulations in swine

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Cytolytic Function for Pseudorabies Virus-Stimulated Porcine CD4+CD8dull+Lymphocytes

Cited by 34 publications

References 37 publications

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

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

Genome-wide association study for T lymphocyte subpopulations in swine

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Product

Resources

About

Cytolytic Function for Pseudorabies Virus-Stimulated Porcine CD4⁺CD8^dull+Lymphocytes