Porcine T lymphocytes and NK cells--an update.
ABSTRACT Natural killer (NK) cells represent an important cell population of the innate immune system with the ability to attack spontaneously pathogen-infected and malignant body cells as well as to produce immune-regulatory cytokines. T lymphocytes belong to the adaptive immune system and perform a wide array of functions in immune regulation, inflammation and protective immune responses. In this review we summarize the current knowledge about the phenotype and functional characteristics of these two cell populations in swine. Porcine NK cells can be distinguished from T cells by the complex phenotype perforin+ CD3(-)CD4(-)CD5(-)CD6(-)CD8alpha+CD8beta(-)CD11b+CD16+. Investigations so far show that these cells have the capacity to lyse virus-infected target cells and respond to various regulatory cytokines. Such cytokines can induce interferon-gamma (IFN-gamma) production in porcine NK cells, as well as the up-regulation of effector/activation molecules like perforin and CD25. Porcine T cells can be divided into a number of subpopulations, including a prominent fraction of T cells expressing T-cell receptors (TCR) with gammadelta-chains. Like TCR-alphabeta T cells, these TCR-gammadelta T cells can express CD8alpha and MHC class II, two molecules which in swine seem to be correlated with an activation status of T cells. Functional properties of these cells seem to include cytolytic activity as well as antigen presentation; however, both aspects require further investigation. Like in other species, TCR-alphabeta T cells in swine comprise MHC class-I restricted cytolytic T cells, T-helper cells and recently identified regulatory T cells. We summarize data on the phenotype and function of these cells including memory cell formation. Current knowledge suggests that MHC class-I restricted cytolytic T cells can be identified by the expression of CD8alphabeta heterodimers. T-helper cells express CD4 as well as other activation-related markers, including CD8alpha, MHC class II and CD45RC. Porcine regulatory T cells have a phenotype similar to that of mouse and humans: CD4+CD25+Foxp3+. First results indicate that these cells can suppress proliferation of other T cells and produce IL-10. Finally, the abundant expression of swine-specific activation markers CD8alpha and MHC class II on T cells and NK cells is discussed in more detail.
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ABSTRACT: Hybridomas were produced from fusions of the SP2/0 mouse myeloma with splenic cells from: 1) an outbred Sprague Dawley rat immunized with swine peripheral blood mononuclear (PBM) cells; 2) a (CBA/NDub X BALB/c Dub) F1 mouse immunized with concanavalin A (Con A) activated swine PBM cells and 3) a (BALB/c Dub X C3H/He Dub) F1 mouse immunized with swine thymocytes. The resulting supernatants were screened by a microcytotoxicity assay for activity against swine PBM cells. Four hybridomas (MSA1, MSA2, MSA3 and MSA4) were selected, cloned and characterized by their cell reactivity and effect on mitogenic assays. MSA1 and MSA2 belong to the rat IgG2b subclass. MSA3 and MSA4 are of the mouse IgG2a subclass. These monoclonal antibodies reacted in the following manner: MSA1 with monocytes, granulocytes, red blood cells and bone marrow cells; MSA2 with subset of T cells; MSA3 with B cells and subsets of T cells and monocytes (class II molecule) and MSA4, a pan-T cell reagent (E-rosette receptor). The involvement of the various cell types reactive to the different monoclonal antibodies in the mitogenic response of swine PBM cells to Con A, phytohemagglutinin (PHA) or pokeweed mitogen (PWM) was investigated by cellular depletion with monoclonal antibody plus complement. Cellular depletion of PBM cells with the following monoclonal antibodies plus complement treatment resulted in: MSA1, almost total reduction in the mitogenic response to low doses of Con A or PWM; MSA2, partial reduction in the proliferative responses to any concentration of Con A, PHA or PWM; MSA3, partial reduction in proliferative responses to low concentrations of Con A or PWM and 4) MSA4, total elimination of any proliferative response to Con A, PHA or PWM.Veterinary Immunology and Immunopathology 03/1986; 11(2):107-21. · 1.88 Impact Factor
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ABSTRACT: The aim of the present study was to investigate at 2, 4, and 6 weeks after birth cytokine expression by peripheral blood mononuclear cells and bronchial lymph node cells from piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). Technically, by flow cytometry we were able to measure gamma interferon (gamma-IFN), tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4), and IL-8 levels. In general, we found increases in the percentages of IL-4-, gamma-IFN-, and TNF-alpha-producing lymphocytes in the infected piglets compared to the percentages in the uninfected control animals, while there was a decrease in the percentage of IL-8-producing monocytes. We believe that these findings reflect a general lymphocyte activation stage that is created due to the infection and that occurs in combination with impairment of the monocyte function, possibly due to the ongoing viral replication in these cells. Single-cell bronchial lymph node preparations exhibited very much the same cytokine profiles as peripheral blood mononuclear cells except for a lack of IL-8 production. When the levels of the individual cytokines in the three groups of PRRSV-infected piglets were compared, the levels of cytokine expression at 4 weeks diverged from those at 2 and 6 weeks, in that there was a significant decrease in the numbers of lymphocytes producing gamma-IFN and TNF-alpha. This tendency was also observed among blood monocytes and lymph node macrophages. Possible reasons for this temporary immunosuppression in the piglets at 4 weeks are discussed.Clinical and Diagnostic Laboratory Immunology 12/2002; 9(6):1229-34. · 2.51 Impact Factor
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ABSTRACT: T-cell epitopes within viral polypeptide VP4 of the capsid protein of foot-and-mouth disease virus were analyzed using 15-mer peptides and peripheral blood mononuclear cells (PBMC) from vaccinated outbred pigs. An immunodominant region between VP4 residues 16 and 35 was identified, with peptide residues 20 to 34 (VP4-0) and 21 to 35 (VP4-5) particularly immunostimulatory for PBMC from all of the vaccinated pigs. CD25 upregulation on peptide-stimulated CD4(+) CD8(+) cells-dominated by Th memory cells in the pig-and inhibition using anti-major histocompatibility complex class II monoclonal antibodies indicated recognition by Th lymphocytes. VP4-0 immunogenicity was retained in a tandem peptide with the VP1 residue 137 to 156 sequential B-cell epitope. This B-cell site also retained immunogenicity, but evidence is presented that specific antibody induction in vitro required both this and the T-cell site. Heterotypic recognition of the residue 20 to 35 region was also noted. Consequently, the VP4 residue 20 to 35 region is a promiscuous, immunodominant and heterotypic T-cell antigenic site for pigs that is capable of providing help for a B-cell epitope when in tandem, thus extending the possible immunogenic repertoire of peptide vaccines.Journal of Virology 06/2000; 74(10):4902-7. · 5.08 Impact Factor