INTRODUCTION: Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue. BACKGROUND AND OBJECTIVE: We have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. METHODS: We tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. RESULTS: Both the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. DISCUSSION AND CONCLUSION: The results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.

• MeSH
• atenuované vakcíny MeSH
• imunitní systém MeSH
• prasata MeSH
• protilátky virové MeSH
• reprodukční a respirační syndrom prasat * prevence a kontrola   MeSH
• virus reprodukčního a respiračního syndromu prasat * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Studies in humans and mice indicate the critical role of the surrogate light chain in the selection of the productive immunoglobulin repertoire during B cell development. However, subsequent studies using mutant mice have also demonstrated that alternative pathways are allowed. Our recent investigation has shown that some species, such as pig, physiologically use preferential rearrangement of authentic light chains, and become independent of surrogate light chains. Here we summarize the findings from swine and compare them with results in other species. In both groups, allelic and isotypic exclusions remain intact, so the different processes do not alter the paradigm of B-cell monospecificity. Both groups also retained some other essential processes, such as segregated and sequential rearrangement of heavy and light chain loci, preferential rearrangement of light chain kappa before lambda, and functional κ-deleting element recombination. On the other hand, the respective order of heavy and light chains rearrangement may vary, and rearrangement of the light chain kappa and lambda on different chromosomes may occur independently. Studies have also confirmed that the surrogate light chain is not required for the selection of the productive repertoire of heavy chains and can be substituted by authentic light chains. These findings are important for understanding evolutional approaches, redundancy and efficiency of B-cell generation, dependencies on other regulatory factors, and strategies for constructing therapeutic antibodies in unrelated species. The results may also be important for explaining interspecies differences in the proportional use of light chains and for the understanding of divergences in rearrangement processes. Therefore, the division into two groups may not be definitive and there may be more groups of intermediate species.

• MeSH
• alely MeSH
• B-lymfocyty MeSH
• geny pro imunoglobuliny * MeSH
• imunoglobuliny - kappa-řetězce * genetika   MeSH
• myši MeSH
• náhradní lehké řetězce imunoglobulinů genetika   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Porcine thymus contains three independent populations of cells that have rearranged immunoglobulin heavy chain VDJH genes. The first population can be found exclusively in medulla and it consists of existing mature B cells and plasma cells. The second consists of developing B cells characterized by the presence of selected VDJH rearrangement, similar to B cell lymphogenesis in the bone marrow. The third population is entirely unaffected by selection mechanism for productive VDJH rearrangement and represents T lineage cells that rearrange immunoglobulin genes. Transcription of unselected VDJH repertoire is not allowed in T cells. Sequence analysis of unselected VDJH repertoire from T cells also revealed important consequences for B cell lymphogenesis and selection of B cell repertoire. As far as we know, this is the first evidence that some species completely rearrange VDJH genes in T cells. Our results also support the finding that B cells actively develop in the thymus.

• MeSH
• B-lymfocyty imunologie   MeSH
• druhová specificita MeSH
• geny pro těžké řetězce imunoglobulinů genetika   MeSH
• lidé MeSH
• plod imunologie   MeSH
• podskupiny lymfocytů imunologie   MeSH
• prasata genetika   růst a vývoj   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• thymus růst a vývoj   imunologie   MeSH
• V(D)J rekombinace genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development. We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces "holes" in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens. The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens. Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies. Generation of cytotoxic and regulatory T cells may also be impaired. Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by "last ditch" polyclonal B cell activation. In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a "red herring" that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis. Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGFβ which stimulates development of regulatory T cells (Tregs).

• MeSH
• hypergamaglobulinemie krev   etiologie   metabolismus   MeSH
• imunoglobulinové izotypy krev   imunologie   MeSH
• interakce hostitele a patogenu imunologie   MeSH
• náchylnost k nemoci MeSH
• pandemie MeSH
• prasata MeSH
• protilátky virové krev   imunologie   MeSH
• reprodukční a respirační syndrom prasat krev   epidemiologie   etiologie   MeSH
• T-lymfocyty cytologie   imunologie   metabolismus   MeSH
• thymocyty cytologie   imunologie   metabolismus   MeSH
• thymus imunologie   metabolismus   MeSH
• virus reprodukčního a respiračního syndromu prasat fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The adaptive immune system of higher vertebrates is believed to have evolved to counter the ability of pathogens to avoid expulsion because their high rate of germline mutations. Vertebrates developed this adaptive immune response through the evolution of lymphocytes capable of somatic generation of a diverse repertoire of their antigenic receptors without the need to increase the frequency of germline mutation. The focus of our research and this article is on the ontogenetic development of the lymphocytes, and the repertoires they generate in swine. Several features are discussed including (a) the "closed" porcine placenta means that de novo fetal development can be studied for 114 days without passive influence from the mother, (b) newborn piglets are precocial permitting them to be reared without their mothers in germ-free isolators, (c) swine are members of the γδ-high group of mammals and thus provides a greater opportunity to characterize the role of γδ T cells and (d) because swine have a simplified variable heavy and light chain genome they offer a convenient system to study antibody repertoire development.

• MeSH
• adaptivní imunita * MeSH
• B-lymfocyty imunologie   MeSH
• gastrointestinální trakt imunologie   MeSH
• genetická variace MeSH
• imunogenetické jevy MeSH
• imunoglobuliny genetika   MeSH
• lidé MeSH
• lymfoidní progenitorové buňky fyziologie   MeSH
• modely u zvířat MeSH
• prasata MeSH
• receptory antigenů genetika   MeSH
• sekvence nukleotidů MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The ileal Peyers patches (IPP) of newborn germfree (GF) piglets were isolated into blind loops and the piglets colonized with a defined probiotic microflora. After 5 weeks, IgA levels in the intestinal lavage (IL) of loop piglets remained at GF levels and IgM comprised ∼70% while in controls, IgA levels were elevated 5-fold and comprised ∼70% of total Igs. Loop piglets also had reduced serum IgA levels suggesting the source of serum IgA had been interrupted. The isotype profile for loop contents was intermediate between that in the IL of GF and probiotic controls. Surprisingly, colonization alone did not result in repertoire diversification in the IPP. Rather, colonization promoted pronounced proliferation of fully switched IgA(+)IgM(-) B cells in the IPP that supply early, non-diversified "natural" SIgA antibodies to the gut lumen and a primary IgA response in serum.

• MeSH
• aktivace lymfocytů MeSH
• B-lymfocyty fyziologie   MeSH
• buněčná diferenciace MeSH
• gnotobiologické modely MeSH
• ileum imunologie   MeSH
• imunoglobulin A sekreční genetika   MeSH
• imunoglobulin M genetika   MeSH
• imunologická paměť MeSH
• kultivované buňky MeSH
• novorozená zvířata MeSH
• Peyerovy pláty imunologie   MeSH
• prasata imunologie   MeSH
• přesmyk imunoglobulinových tříd MeSH
• probiotika aplikace a dávkování   MeSH
• proliferace buněk MeSH
• rozmanitost protilátek MeSH
• střevní mikroflóra imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

• MeSH
• apoptóza MeSH
• Artiodactyla imunologie   MeSH
• B-lymfocyty cytologie   imunologie   MeSH
• buněčný rodokmen MeSH
• bursa Fabricii cytologie   imunologie   chirurgie   MeSH
• druhová specificita MeSH
• gnotobiologické modely MeSH
• imunitní systém embryologie   růst a vývoj   MeSH
• králíci imunologie   MeSH
• kur domácí imunologie   MeSH
• lidé MeSH
• lymfatické uzliny cytologie   imunologie   MeSH
• lymfoidní tkáň cytologie   imunologie   chirurgie   MeSH
• lymfopoéza MeSH
• mezenterium imunologie   MeSH
• modely imunologické MeSH
• Peyerovy pláty cytologie   imunologie   chirurgie   MeSH
• prasata imunologie   MeSH
• savci embryologie   imunologie   MeSH
• střeva imunologie   MeSH
• střevní sliznice embryologie   růst a vývoj   imunologie   MeSH
• tvorba protilátek MeSH
• zvířata MeSH
• Check Tag
• králíci imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Based on studies of sheep, ileal Peyer's patches (IPP) have been regarded as a type of primary lymphoid tissue similar to the bursa of Fabricius in chicken. Because bursectomy results in B cell deficiency, we wondered whether resection of the IPP of piglets would have a similar effect. Comparison of IPP-resected, surgical shams and untreated germ-free piglets, all of which were later colonized with a defined commensal flora, demonstrated that resection of the IPP did not alter the level and phenotype of B and T cells in lymphoid tissues and the blood 10 wk after surgery. Additionally, colonization of IPP caused a shift from the fetal type of lymphocyte distribution to the adult type that is characterized by prevalence of B cells, with many of them representing IgA(+) switched B cells or displaying a more mature CD2(-)CD21(+) and CD2(-)CD21(-) phenotype. Moreover, colonization leads to appearance of effector CD4(+)CD8(+) αβ T helper and CD2(+)CD8(-) γδ T cells. Comparison of germ-free with colonized pigs and experiments utilizing surgical transposition of jejunal Peyer's patch into terminal ileum or construction of isolated ileal loops indicated that lymphocyte development in IPP is dependent on colonization. Although our studies confirmed higher mitotic and apoptotic rates in IPP, they failed to identify any cell populations that resemble developing B lineage cells in the bone marrow. These results indicate that porcine IPP are not required for systemic B cell generation or maintenance, but they are secondary lymphoid tissue that appears important in immune responses to colonizing bacteria.

• MeSH
• buněčná diferenciace imunologie   MeSH
• buněčný rodokmen imunologie   MeSH
• gnotobiologické modely MeSH
• ileum cytologie   imunologie   chirurgie   MeSH
• lymfopoéza imunologie   MeSH
• novorozená zvířata MeSH
• Peyerovy pláty cytologie   imunologie   chirurgie   MeSH
• počet lymfocytů MeSH
• podskupiny B-lymfocytů cytologie   imunologie   metabolismus   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• srovnávací studie MeSH

• MeSH
• B-lymfocyty fyziologie   MeSH
• genová přestavba MeSH
• plod imunologie   MeSH
• prasata imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• fyziologie
• alergologie a imunologie