Outbreaks of porcine reproductive and respiratory syndrome virus (PRRSV) in vaccinated sow herds from occurrence to stabilization were monitored and analyzed in terms of serology and reproductive performance. Three different conventional pig farms experienced severe reproductive failures with the introduction of a type 1 PRRSV. These farms had adopted mass vaccination of sows using a type 2 PRRSV modified live vaccine (MLV). Therefore, to control the type 1 PRRSV, an alternative vaccination program utilizing both type 1 and type 2 MLV was undertaken. Following whole herd vaccinations with both types of MLV, successful stabilization of PRRS outbreaks was identified based on serological data (no viremia and downward trends in ELISA antibody titers in both sows and suckling piglets) and recovery of reproductive performance. Additionally, through comparison of the reproductive parameters between outbreak and non-outbreak periods, it was identified that PRRSV significantly affected the farrowing rate and the number of suckling piglets per litter at all three pig farms. Comparison of reproductive parameters between periods when the different vaccination strategies were applied revealed that the number of piglets born in total and born dead per litter were significantly increased after the introduction of the type 1 PRRS MLV.
Agriculture ; Disease Outbreaks ; Enzyme-Linked Immunosorbent Assay ; Immunity, Herd ; Immunity, Heterologous ; Mass Vaccination ; Porcine Reproductive and Respiratory Syndrome ; Porcine respiratory and reproductive syndrome virus ; Vaccination ; Viremia

Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506) are broadly used in organ transplantations as immune suppressants. As the calcineurin/NFAT signaling pathway has been identified as critical pathway in the interleukin-2 (IL-2) production of T cells, inhibition of T-cell derived IL-2 has been considered the major mechanism of calcineurin inhibitors. However, there is increasing evidence that NFAT transcription factor is involved in multiple functions of dendritic cells and innate immune cells as well. NFAT expression is not restricted to T cells, and IL-2 can be produced in dendritic cells and macrophages through the calcineurin/NFAT pathway. Furthermore, it has been discovered that NFAT regulates expressions of several inflammatory mediators, including TNF-α and cyclooxygenase-2 in innate immune cells. Therefore, calcineurin inhibitors may have much broader effects in the transplant recipients than previously being considered. In this review, we reviewed recently discovered roles of NFAT pathway in dendritic cells and innate immune cells, and discussed positive and negative implications of calcineurin inhibitors' broader effects with a focus on islet xenotransplantation.
Calcineurin ; Critical Pathways ; Cyclooxygenase 2 ; Cyclosporine ; Dendritic Cells* ; Immunity, Innate ; Interleukin-2 ; Islets of Langerhans Transplantation ; Macrophages ; Organ Transplantation ; T-Lymphocytes ; Tacrolimus ; Transcription Factors ; Transplantation ; Transplantation, Heterologous* ; Transplants

PURPOSE: Shortage of donor organs is one of the major barriers of clinical organ transplantation. To overcome the shortage, a huge amount of research into xenotransplantation has been done worldwide. The major problem in xenotransplantation is hyperacute rejection, a rapid and violent rejection that damages the graft within minutes or hours. Hyperacute rejection is mediated by the components of natural immunity, most notably natural antibodies and complements. METHODS: The aim of this study is to explore the quantitative amounts of the natural antibodies and complements in the sera of patential recipients with respect to their diseases. The samples of blood from the 10 patients with end stage renal or liver disease were obtained for the assay of natural xenoreactive antibodies. Natural anti-porcine endothelial antibodies (IgM and IgG) were measured by ELISA with porcine aortic endothelial cells in culture as targets. Quantitative analysis of C3 was also done with the ELISA with porcine endothelial cell in culture. RESULTS: Optical densities measured with the ELISA for IgM or IgG natural antibodies in the blood from the different three groups (healthy volunteer, renal failure patients, and liver failure patients) to cultured porcine aortic endothelial cells were not statistically (P>0.05) different among the three groups. Moreover, those for complement (C3) to porcine endothelial cells were not statistically (P>0.05) different among the groups. CONCLUSION: Further efforts should be made toward modifying the technique for removal of specific natural antibodies and complements for the successful xenotransplantation regardless the disease entities of potential recipient candidates.
Antibodies ; Complement System Proteins* ; Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunity, Innate ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins* ; Kidney Failure, Chronic* ; Liver Diseases ; Liver Failure* ; Liver* ; Organ Transplantation ; Renal Insufficiency ; Tissue Donors ; Transplantation, Heterologous ; Transplants ; Volunteers

BACKGROUND: The major problem in transplants between widely disparate species is hyperacute rejection, a rapid and violent rejection that damages the graft within minutes or hours. Hyperacute rejection is mediated by the components of natural immunity, most notably natural antibodies and complements. The absorption of natural antibodies on endothelial cells by passing the recipient's blood through a donor kidney or liver is very effective in removing xenoreactive natural antibodies from a recipient's blood. To modify hyperacute rejection in a pig-to-dog renal transplant, we transplanted a porcine kidney, which had been perfused after organ perfusion of canine blood through a pig's liver and kidney, was transplanted en-bloc with the kidney. METHODS: The en-bloc organ procurement from male pigs weighing 15-20 kg, including the liver and two kidneys, was performed after perfusion with a cold Euro-Collins solution through the aorta and portal vein. The harvested organs were vascularized to male dogs weighing 25-30 kg by anastomosis of the graft aorta to the recipient's infrarenal aorta, the graft inferior vena cava to the recipient's infrarenal inferior vena cava, and the graft portal vein to the recipient's portal vein with a end-to-side fashion. The recipient's blood was perfused into the liver and one kidney, and then into the other kidney 60 minutes later. During the procedure, the recipient's blood was sampled and assayed for natural xenoreactive antibodies. Natural anti-porcine endothelial antibodies were measured by ELISA with porcine aortic endothelial cells in the culture as targets. Each grafted organ was biopsied serially at 2, 4, 6, 8, 10, 20, 40, and 60 minutes after reperfusion for light microscopic and immunofluorescent examinations. RESULTS: Natural anti-porcine endothelial antibody levels(both IgM and IgG) of canine serum decreased at 60 minutes after organ perfusion of canine blood through a porcine liver and one kidney. Hyperacute rejection (capillary congestion, interstitial hemorrhage, thrombosis, etc.) of the kidneys appeared within20 minutes after blood perfusion regardless of organ absorption of natural antibodies through the porcine liver and one kidney. The appearance of interstitial hemorrhage and thrombosis of the kidney was delayed about 4-10 minutes by organ absorption of natural antibodies. However, acute tubular necrosis appeared early and more obviously in the second kidneys. Immunofluorescence showed granular deposits of canine IgM and IgG in the glomerular mesangium and on the microvessels. Canine IgM, but not IgG, deposition on the second kidney decreased after organ absorption of natural antibodies. Complement deposition was not altered by organ absoption. CONCLUSIONS: The organ perfusion of canine blood through a porcine liver and kidney was effective for only a short time in decreasing the natural anti-porcine endothelial IgM and IgG antibodies of canine serum, and histologic changes appeared in the second kidney of a slightly later time than in the kidney used in antibody absorption. Further efforts should be made toward modifying the technique for removal of specific natural antibodies and complements.
Absorption ; Animals ; Antibodies ; Aorta ; Complement System Proteins ; Dogs ; Endothelial Cells ; Enzyme-Linked Immunosorbent Assay ; Estrogens, Conjugated (USP) ; Fluorescent Antibody Technique ; Glomerular Mesangium ; Hemorrhage ; Heterografts* ; Humans ; Immunity, Innate ; Immunoglobulin G ; Immunoglobulin M ; Kidney* ; Liver* ; Male ; Microvessels ; Necrosis ; Perfusion* ; Portal Vein ; Reperfusion ; Swine ; Thrombosis ; Tissue and Organ Procurement ; Tissue Donors ; Transplantation, Heterologous ; Transplants ; Vena Cava, Inferior

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41+/-2.77% vs. 55.02+/-5.44%, p=0.027) and cell lysis (42.95+/-1.75% vs. 87.99 +/-2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs.
Animals ; Antibodies, Heterophile/immunology ; Antibody Formation/*immunology ; Antigens, CD40/immunology ; Aorta/cytology ; Cell Line, Transformed ; Cell Survival/immunology ; Complement Membrane Attack Complex/immunology ; Complement System Proteins/immunology ; Dendritic Cells/cytology/immunology ; Endothelial Cells/cytology/immunology ; Epitopes/immunology ; Humans ; Immune Tolerance/*immunology ; Immunity, Cellular/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Sertoli Cells/cytology/*immunology ; Swine ; *Tissue Engineering ; Transplantation, Heterologous