RESUMEN
Porcine CD8(+) lymphocytes are critical for the development of cellular immune responses to bacterial (i.e. CD8alphaalpha(+)) and viral (i.e. CD8alphabeta(+) lymphocytes) pathogens. Vaccination and challenge modulate the kinetics of appearance of CD8(+) cells in peripheral blood. In addition to antigen-mediated modulation, nutritional modulation can also influence cell-mediated immunity. We had previously observed that diets supplemented with a mixture of conjugated linoleic acid (CLA) isomers expanded porcine CD8(+) peripheral blood mononuclear cells (PBMC). The present study aimed to investigate the influence of prior consumption of a nutraceutical, (i.e. dietary CLA) on phenotypes and effector functions of porcine PBMC following immunization with a bacterin or a modified-live viral vaccine. It was demonstrated that the effects of dietary CLA on immune cell phenotype (i.e. numbers of CD8alphabeta(+) cells) persisted after the compound was withdrawn from the diet (i.e. 67 days), whereas effector functions (i.e. antigen-stimulated proliferation and cytotoxicity) disappeared earlier (i.e. 25 days). Specifically, numbers of CD8alphabeta(+) PBMC in pigs that had been fed diets supplemented with CLA were greater than in pigs fed control (i.e. isoenergetic and unsupplemented) diets, regardless of the vaccination treatment. Furthermore, prior dietary CLA supplementation interacted with viral immunization (i.e. modified-live pseudorabies virus (PRV) vaccine) by enhancing both pseudorabies-specific proliferative responses of CD8alphabeta(+) PBMC and granzyme activities of PBMC.
Asunto(s)
Antígenos Bacterianos/inmunología , Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Ácidos Linoleicos/administración & dosificación , Animales , Apoptosis , Suplementos Dietéticos , Granzimas , Inmunofenotipificación , Activación de Linfocitos , Fenómenos Fisiológicos de la Nutrición , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Serina Endopeptidasas/metabolismo , PorcinosRESUMEN
In vivo vaccination and challenge studies have demonstrated that CD8(+) lymphocytes are essential for the development of cell-mediated protection against intracellular pathogens and neoplastic cells. Depletion of peripheral blood CD8(+) cells interferes with clearance of viruses and intracellular fungi, induction of delayed type hypersensitivity responses and antitumoral activity. In contrast to humans or mice, porcine peripheral CD8(+) lymphocytes are characterized by a heterogeneous expression pattern (i.e., CD8alphabeta and CD8alphaalpha) that facilitates the study of distinctive traits among minor CD8(+) cell subsets. A factorial (2 x 2) arrangement within a split-plot design, with 16 blocks of two littermate pigs as the experimental units for immunization treatment (i.e., unvaccinated or vaccinated with a proteinase-digested Brachyspira hyodysenteriae bacterin) and pig within block as the experimental unit for dietary treatment (soybean oil or conjugated linoleic acid) were used to investigate the phenotypic and functional regulation of CD8(+) cells by dietary conjugated linoleic acid (CLA). Dietary CLA supplementation induced in vivo expansion of porcine CD8(+) cells involving T-cell receptor (TCR)gammadeltaCD8alphaalpha T lymphocytes, CD3(-)CD16(+)CD8alphaalpha (a porcine natural killer cell subset), TCRalphabetaCD8alphabeta T lymphocytes and enhanced specific CD8(+)-mediated effector functions (e.g., granzyme activity). Expansion of peripheral blood TCRalphabetaCD8alphabeta cells was positively correlated (r = 0.89, P < 0.01) with increased percentages of CD8alphabeta(+) thymocytes. Functionally, CLA enhanced the cytotoxic potential of peripheral blood lymphocytes and proliferation of TCRgammadeltaCD8alphaalpha cells. Collectively, these results indicate that dietary CLA enhances cellular immunity by modulating phenotype and effector functions of CD8(+) cells involved in both adaptive and innate immunity.
Asunto(s)
Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/fisiología , Dieta , Ácido Linoleico/administración & dosificación , Porcinos/fisiología , Animales , Vacunas Bacterianas/inmunología , Linfocitos T CD4-Positivos/fisiología , Linfocitos T CD8-positivos/citología , División Celular/efectos de los fármacos , Células Asesinas Naturales/citología , Ácido Linoleico/farmacología , Subgrupos Linfocitarios/citología , Monocitos/enzimología , Fenotipo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Serina Endopeptidasas/sangre , Spirochaetales/metabolismo , Infecciones por Spirochaetales/prevención & control , Linfocitos T Reguladores/efectos de los fármacos , Timo/citología , VacunaciónRESUMEN
Early-weaned pigs (n = 64) averaging 5.3 +/- 0.3 kg and distributed into two environments (dirty and clean) were used to evaluate effects of conjugated linoleic acid (CLA) on growth performance, immune competence, and empty body composition. A factorial (2 x 4) arrangement within a split-plot design, with four littermate pigs as the experimental unit for the environment, pig within litter as the experimental unit for dietary treatment, and d-0 body weight used as covariate, were used in data analysis. Diets were formulated to contain CLA at 0, 0.67, 1.33, or 2% and to exceed the NRC (1988) nutrient needs of pigs. Animals were given ad libitum access to feed for 7 wk in three phases (I, 1 to 2; II, 3 to 5; and III, 6 to 7 wk). Within phases, diets were isocaloric and isonitrogenous. In Phase I, as dietary CLA concentration increased, ADG and ADFI decreased linearly (P < 0.05 and P < 0.02, respectively). In Phase II, upon adaptation to dietary CLA supplementation, ADG increased quadratically (603, 623, 622, and 548 g/d; P < 0.01), ADFI decreased linearly (873, 840, 867, and 717 g/d; P < 0.02) and gain:feed ratio tended to increase linearly (691, 742, 715, and 763; P < 0.07). In Phase III, no differences in growth performance were attributed to either dietary or environmental treatments. The poor health status associated with the dirty environment induced a growth suppression; pigs in the clean room had a greater cumulative ADG (P < 0.01) and ADFI (P < 0.01) than pigs in the dirty room. In Phase I, lower plasma urea nitrogen levels observed in pigs found in the dirty room (P < 0.03) indicated a lower protein intake caused by a lower ADFI. The effects of dietary CLA on peripheral phenotypic profiles of lymphoytes did not appear until d 42. However, as indicated by the growth suppression of pigs in the dirty room, the negative effects of the environmental challenge on pig health and growth had already appeared during phase I. On d 42, CLA induced a linear increase in percentages of CD8+ lymphocytes (21.7, 22.3, 28.0, and 32.7%; P < 0.001). These data suggest that a 42-d dietary CLA supplementation preceding a disease challenge could have prevented disease-associated growth suppression. Also, CLA-mediated amelioration of particular infectious diseases will depend on which CD8+ T cell subset (i.e., CD8alphaalpha-immunoregulatory or CD8alphabeta-cytotoxic) is most influenced by dietary CLA supplementation.
Asunto(s)
Composición Corporal , Grasas de la Dieta/farmacología , Vivienda para Animales , Ácido Linoleico/farmacología , Linfocitos/fisiología , Porcinos/crecimiento & desarrollo , Porcinos/inmunología , Alimentación Animal , Animales , Animales Lactantes/crecimiento & desarrollo , Nitrógeno de la Urea Sanguínea , Vivienda para Animales/normas , Recuento de Leucocitos , Linfocitos/inmunología , Fenotipo , DesteteRESUMEN
Two experiments with weanling pigs were conducted to study the effects on growth and immune responses of excess dietary L-leucine (LEU) and dietary supplementation with the LEU catabolites, alpha-ketoisocaproic acid (KIC) and beta-hydroxymethyl butyrate (HMB). In Exp. 1, 80 pigs were randomly allocated according to initial BW and ancestry to five replications of four dietary treatments (four pigs/pen). The control diet contained wheat, oat groats, menhaden fish meal, and dried whey and provided 1.12% LEU. Treatment diets were the control plus 1.12% LEU, 1.12% KIC, or .4% HMB. The experiment lasted 6 wk. In Exp. 2, 36 pigs were randomly allocated to nine replications of four dietary treatments in a 2 x 2 factorial arrangement. Treatments consisted of two concentrations of dietary LEU and a daily i.m. injection of dexamethasone (DEX) or saline. Pigs were fed a control corn-soybean meal and dried whey diet (1.56% LEU) or the control diet plus 1.56% of crystalline LEU. Pigs were individually penned and the experiment lasted 4 wk. Growth performance, plasma free amino acids, plasma urea nitrogen, and humoral and cellular immune responses were measured. Results indicated that LEU concentrations in practical diets and supplementation with KIC and HMB (Exp. 1) did not detrimentally affect growth and immune response. The high LEU concentration and DEX injection used in Exp. 2, however, were detrimental to both growth and immune response.