Relevance of maintenance triple-drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation.

Immunosuppressive therapy required to treat rejection after lung transplantation (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [WKY] rats) we analyzed the influence of acute CMV infection on postoperative day (POD) 3, with application of standard triple-drug immunosuppression (TD-IS) (cyclosporin A, azathioprine, prednisolone) on late outcome after LTx. Native right lungs and syngeneic grafts (WKY to WKY) served as controls.

Development of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment.

Background: Chronic allograft failure represents the major cause of late morbidity and mortality after solid organ transplantation. Despite the pathological and clinical changes of this disease being well-described, the etiology and the causative factors are still under discussion. Several clinical, as well experimental studies, emphasize the significance of acute rejection.

Allograft conduit wall calcification in a model of chronic arterial graft rejection.

Early allograft vascular wall degeneration has emerged as a major important complication in young patients. To explain this mechanism, we reviewed studies on explants of allograft valved conduits implanted heterotopically into the infrarenal aorta in inbred rats (LEW; RT1I and CAP-RT1C). The following strain combinations (isografts and allografts) were used: syngeneic, LEW- > LEW, strongly allogeneic, and CAP > LEW (RT1- and non-RT1-incompatible).

Short-course cyclosporin A therapy for definite allograft valve survival immunosuppression in allograft valve operations.

This study was designed to determine the effect of short-course cyclosporin A therapy (10 mg/kg daily for 14 days) on allograft valve survival across the histocompatibility barriers in the following rat models; (1) syngeneic Lewis to Lewis (herein referred to as autografts), (2) weakly allogeneic AS to Lewis (RT1 compatible, non-RT1-incompatible), and (3) strongly allogeneic CAP to Lewis (RT1 and non-RT1-incompatible). Cyclosporin A-treated and untreated recipient animals (Lewis) received allovital and antibiotic-treated viable allografts implanted into the infrarenal aorta. Second-set skin grafting was performed 3 weeks after heterotopic valve implantation to test for immunogenicity and presensitization.

Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: morphology.

Several morphological and functional properties of microglial cells, the resident immunoeffector cells of the central nervous system (CNS), differ from those of monocytes/macrophages in other tissues. Microglia are assumed to derive from myelonocytic lineage, possibly as a distinct subpopulation that diverges from a common cell line early in ontogeny, invades the CNS, proliferates, and differentiates into ameboid and then ramified microglia. We tested the hypothesis that some morphological and functional properties of microglia are induced in myelomonocytic cells by nervous tissue, specifically astrocytes.

Ultrastructural studies of acute rejection following single lung transplantation in the rat--histological and immunohistological findings.

Nowadays the acute and especially chronic lung rejection are the major problems after lung transplantation (L-Tx) with relevant influence on longterm survival. We performed lung transplantation in rats to study a possible role of ultrastructural lesions in the graft during the acute rejection process, concerning their reversibility/irreversibility and influence of the chronic rejection. Based on histologic and immunohistologic studies after L-Tx in MHC-different and strong reactive rat strain combination AVN-LEW and filial generation (AVN-LEW)F1-LEW (n = 57 and n = 32) electronmicroscopic studies (TEM, SEM) were performed in the combination AVN-LW (n = 20) on postoperative day 0, 1, 2 and 5, all without immunsuppressive therapy.

Injection of v-mos-transformed and irradiated macrophages leads to longlasting specific acceptance of MHC-allogeneic heart grafts and specific prolongation of skin graft survival in mice.

In vitro studies have revealed that the v-mos-transformed clone mos2 (mos2) of the murine macrophage cell line P388D1 (D1) (H-2d) is capable of inducing a state of specific unresponsiveness in MHC-allogeneic unprimed T cells. Here, we present data on the in vivo relevance of these findings. Male C57bl/6 mice (H-2b) were injected i.

Oncogene transformation can induce tolerogenicity in murine macrophages after down-regulation of immunogenicity without altering major histocompatibility complex antigen expression.

In vitro studies on cell lines may allow analyses of the mechanisms of immunogenicity and tolerogenicity in cells. We used a model of oncogenic transformation of an established murine macrophage cell line and report here that one v-mos-transformed clone expressing unaltered high amounts of MHC class I and II antigens does not induce proliferation of unprimed T cells in primary mixed lymphocyte reactions, in sharp contrast to its non-transformed parental cells. Interestingly, this clone induces specific unresponsiveness, as revealed by the lack of responsiveness of MHC-specific T cells when subsequently exposed to the pertinent MHC alloantigens in immunogenic form but unaltered MHC-third party responsiveness of the naive spleen T cells.

Biocompatibility of silicone oil and high-density liquids. An immunologic study.

Silicone oil and high-density liquids can be useful tools in the treatment of complicated retinal detachments. To test whether these substances induce specific and/or unspecific inflammatory responses, we performed immunoassays on 60 rats of two different inbred strains. After sensitization, each rat was injected in the right foot pad with either silicone oil, fluorosilicone oil, perfluorooctane, or perfluoropolyether.

[Immunological reactions against preserved tracheal transplants? Studies on inbred rat strains].

To determine whether chemical (cialit, merthiolate, alcohol, formaldehyde solution) preserved tracheal segments maintain immunogenicity we performed systematic transplantation-immunological investigations using in vivo-, in vitro- and immunohistological tests. In contrast to other authors no indication of residual antigenicity was found. The survival rates after orthotopic grafting of preserved tracheal segments were shortened.

High-dose cytostatic agents in allogeneic bone marrow transplantation: comparison of the engraftment promoting potential.

We investigated the potential of various cytostatic agents for preventing graft rejection following allogeneic bone marrow transplantation. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) F1(CAP x LEW) marrow cells, which are unable to induce a graft-versus-host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte counts.

Effect of post-transplant methotrexate, cyclosporin A and prednisolone on graft rejection after allogeneic bone marrow transplantation.

Methotrexate, cyclosporin A and prednisolone have been shown to improve graft survival rates in solid organ transplantation. However, little is known concerning their capacity to promote lasting engraftment of allogeneic bone marrow. Therefore, we tested these agents in LEW rats receiving MHC-mismatched marrow after pretreatment with a myeloablative dose of busulfan plus different doses of total body irradiation (TBI).

Immunogenicity testing of food proteins: in vitro and in vivo trials in rats.

The immunogenicity of an industrially produced bacterial food protein (single cell protein, SCP) was analyzed in a comparative study. SCP, casein and ovalbumin were injected into or fed to rats. The systemic response was tested in vitro with a lymphocyte transformation test and in vivo with a footpad swelling assay.

Assessment of different preservation and storage conditions on aortic valves: introduction of a quantitative measuring method of the integrity of endothelial cells.

The fate of human allogeneic aortic valves depends mainly on their histological and immunological condition at the time of transplantation. A screening test making novel use of Alcian Blue was used to determine the integrity of endothelial cells as a prerequisite to their function. The dye uptake into the nucleus was measured quantitatively.

Comparison of cyclophosphamide, cytarabine, and etoposide as immunosuppressive agents before allogeneic bone marrow transplantation.

Etoposide and cytarabine have been shown to exert high antileukemic activity and are currently under study as preparatory agents before allogeneic bone marrow transplantation. However, data concerning their engraftment-promoting potency are scarce. Therefore, we tested these agents in LEW rats receiving a myeloablative dose of busulfan followed by transfer of F1 (CAP X LEW) marrow, which is unable to induce a graft-v-host reaction (GVHR).