摘要:

Dendritic cells are now regarded not only as the initiators but also as regulators of immune responses. They are potentially powerful tools for the therapeutic manipulation of immune reactivity in cancer, infectious disease, and allograft rejection. We provide a brief overview of the properties of dendritic cells, with emphasis on recently acquired information, then focus attention on their capacity to modulate immune reactivity, and its relevance to transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.We have previously reported that the early phases of the immune response of rats to hamster xenografts are characterized by the production of IgM xenoantibodies encoded by a restricted group of Ig germline VHgenes (VHHAR family). In the later phases of the reaction, an IgM to IgG isotype switch occurs and our study examines the structure of the rearranged VHHAR genes used to encode IgG antibodies after this isotype switch.Methods.A quantitative polymerase chain reaction was used to investigate the changes in the levels of VHHAR+IgG mRNA seen after xenotransplantation. cDNA libraries specific for VHHAR+Ig γ chain were established from total RNA extracted from splenocytes of naive rats and xenograft recipients of hamster hearts at days 4, 8, 21, and 28 posttransplantation. Colony filter hybridization was used to estimate the relative frequency of the use of individual VHHAR+IgG subclasses. Selected IgG clones from day 21 cDNA libraries were sequenced and analyzed for VH-D-JHgene usage and antibody combining site structure.Results.The level of mRNA for VHHAR+IgG increased 6-fold in xenograft recipients at day 21 post-transplantation when compared with naive animals. The relative frequency of isotype usage for VHHAR+IgG1 antibodies alone increased from 22.3% at day 0 to 37.4% at day 21 PTx. Ten IgG clones from the day 21 cDNA libraries have been sequenced for the rear-ranged VH-D-JHgenes. Thirty percent (3/10) of these IgG clones used VHHAR genes for the coding of heavy chain variable region with limited numbers of nucleic acid substitutions (>98% identity with their germline progenitors) although others demonstrated increased variation in nucleotide sequences (95-97% identity) when compared with germline VHgenes. Analysis of the canonical binding site structure from the predicted amino acid sequences demonstrated that the majority of IgG clones (9/10) displayed a similar pattern of conserved configurations for their combining sites.Conclusions.The change in IgM to IgG antibody production in the later stages of the humoral immune response of rats to hamster xenografts is associated with an IgM to IgG isotype switch and an increased production of antibodies of the IgG1 isotype. Rat anti-hamster IgG xenoantibodies continue to express the VHHAR family of VHgenes, many in their original germline configuration, to encode antibody recognition of the hamster target antigens. There are, however, a majority of antibodies for which the VHgenes express evidence of increased nucleic acid sequence variation when compared to currently available germline sequences. The source of this variation is not known but may represent the expression of as yet unidentified germline genes and/or the introduction of T cell-driven somatic mutations. Despite the appearance of this variation, the unusual level of conservation in key antigen binding sites within the VHregion suggests the variation, independent of its origin, may have a limited influence on the restricted nature of the host antibody response to xenografts.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.BB/Wor rats develop spontaneous autoimmune insulin-requiring diabetes mellitus and lymphocytic thyroiditis (LT). Our investigations examined the effect of the thyroid-specific agents, iodine and methimazole (MMI) on thyroid graft survival in BB/Wor rats, compared the intrathyroidal cytokine mRNA expression of endogenous and engrafted thyroids, and ascertained whether unfractionated splenocytes could protect thyroid grafts from lymphocytic infiltration.Methods.In study 1, 0.025% iodine water-treated LT-prone NB line BB/Wor rats were randomized to receive one of the following treatments: (1) 1.0×108splenocytes, IV from LT-resistant WA line BB/Wor rats, (2) WA rat thyroid transplants, (3) both, or (4) neither (controls). In study 2, after thyroid transplantation, LT-prone BB/Wor rats were randomized to receive (1) WA splenocytes, (2) 0.025% iodine water, (3) 0.05% MMI water or, (4) tap water (controls). The incidence of LT was determined by microscopic inspection after hematoxylin and eosin staining. Lymphocytic infiltrates were characterized by immunohistochemistry. Cytokine mRNA was detected by RT-PCR.Results.Grafts from MMI-treated rats had a significantly lower incidence of lymphocytic infiltration (MMI: 2/5; Tap: 5/5; I 5/5,P<0.05, χ2). IL-10 mRNA was expressed in 77% (7/9) endogenous thyroids and 20% (1/5) of the transplanted WA thyroids (P<0.05, χ2) from iodine-treated rats with LT. There was no difference in IL-12 mRNA expression. Lymphocytic infiltration occurred in 100% of the splenocyte-treated graft recipients. Both endogenous and engrafted thyroids contained CD4 and C8 T cells with scattered IgG staining.Conclusion.Target organ-specific interventions that suppress antigen presentation may have an adjunctive role in transplantation tolerance. The differential expression of IL-10 may indicate preferential Th2 lymphocyte activation in the endogenous tissues.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Intrathymic (IT) administration of antigen when combined with peripheral T-cell depletion has been shown to induce operational tolerance in a wide range of experimental protocols. IT injection of pancreatic islets has been demonstrated not only to induce tolerance to alloantigen but also to prevent the development of autoimmune β-cell destruction in models of type I diabetes. However, little is known about the mechanisms involved in tolerance induction after IT islet injection.Methods and Results.A protocol for the induction of tolerance to fully allogeneic (C57BL/10; H2b) peripheral islet allografts was developed in CBA/Ca (H2k) recipients by the IT injection of allogeneic islets combined with depletion of peripheral CD4+T cells. This protocol was based upon our own data and those of others showing that CD4+T cells play a critical role in islet allograft rejection. Using this regimen, donor-type peripheral islet allografts survived indefinitely whereas third-party grafts were rejected. To determine the fate of alloreactive thymocytes that recognize donor major histocompatibility complex antigens via the direct pathway, T-cell receptor transgenic mice specific for the major histocompatibility complex class I molecule Kb(BM3 and DES) were used as recipients. IT injection of islets expressing the specific alloantigen Kbresulted in clonal deletion of alloreactive thymocytes in T-cell receptor transgenic recipients. No evidence of clonal inactivation in the residual peripheral alloreactive population was observed in this system.Conclusions.IT injection of allogeneic islets and concomitant CD4+T-cell depletion is able to induce donor-specific unresponsiveness. One mechanism responsible for this unresponsiveness is the clonal deletion of thymocytes that recognize alloantigen via the direct pathway.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT).Methods.Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) ROLT, 500 μg/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated.Results.dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that underwent syngeneic ROLT. In the rats that underwent allogeneic ROLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT.Conclusions.Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.ATP resynthesis during reperfusion after liver preservation has been shown to be well correlated with the function of transplanted grafts. Nevertheless, the advantages of a cellular energy charge loading during the preservation period are yet not fully understood. This study evaluates the effects of different nucleotide levels at the end of preservation on metabolic changes and oxidative stress during reperfusion.Methods.Two experimental groups were chosen reflecting different energy charge states after preservation: static cold storage for 10 hr and hypothermic oxygenated oscillating perfusion for 10 hr. In both experimental groups, normothermic ex vivo acellular reperfusion over 40 min was performed. A third group consisted of nonpreserved livers similarly reperfused for 40 min. Superoxide formation was detected by the superoxide dismutase inhibitable reduction of ferricytochrome c added to the normothermic perfusate.Results.Superoxide formation and lipid peroxidation malondialdehyde were significantly lower during reperfusion after the energy charge loading before reperfusion by the hypothermic oscillating perfusion technique. However, oxygen radical formation, liver cell injury (lactate dehydrogenase [LDH] release), and TNFα release were significantly higher in energy charge-depleted groups (nonpreserved and cold stored livers).Conclusions.Hypothermic oscillating oxygenated perfusion led to the elevated energy charge during preservation and led to reduced oxygen radical formation as well as less lipid peroxidation during reperfusion, in contrast to cold stored livers and nonpreserved livers. This suggests a correlation between the energy charge before reperfusion and oxygen radical formation as well as liver injury at reperfusion.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.There appears to be general consensus that a relationship exists between noncompliance and clinical outcomes in health care, including renal transplantation. This study investigated variables associated with medication noncompliance after renal transplantation.Methods.A mail survey containing objective and subjective variables was sent to individuals who met eligibility criteria. Medication compliance was measured by two items: 1) Frequency of forgetting to take medications and 2) Frequency of not taking medications exactly as prescribed. Descriptive and multivariate analyses were utilized to examine the data.Results.Individuals who were older and those who perceived less pain were less likely to forget medications. The belief that health outcomes were controlled by chance and feeling bothered by part of the transplant experience were associated with greater likelihood of forgetting medications. Individuals who perceived a higher level of social functioning and those who believed that health outcomes were controlled by powerful others were more likely to take medications exactly as prescribed. An internal locus of control for health outcomes and feeling bothered by part of the transplant experience were associated with less likelihood of taking medication exactly as prescribed.Conclusions.The finding of this study suggest that compliance with medications after renal transplant is associated with subjective, not objective variables. Positive feelings regarding their physicians and the transplant experience increased compliance. Combining consistent measurement of compliance, examination of its relationship to clinical outcomes, and appreciation for the patient perspective should result in increased levels of compliance and better clinical outcomes.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID