Microchimerism, dendritic cell progenitors and transplantation tolerance

The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow‐derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen‐presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM‐CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T‐dependent areas of host lymphoid tissue, where some at least upregulate cell surface MHC class II. These donor‐derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver. A key finding is that in mice, progeny of these donor‐derived DC progenitors can be propagated ex vivo from the bone marrow and other lymphoid tissues of nonimmunosuppressed spontaneously tolerant liver allograft recipients. In humans, donor DC can also be grown from the blood of organ allograft recipients whose organ‐source chimerism is augmented with donor bone marrow infusion. DC progenitors cannot, however, be propagated from the lymphoid tissue of nonimmunosuppressed cardiac‐allografted mice that reject their grafts. These findings are congruent with the possibility that bidirectional leukocyte migration and donor cell chimerism play key roles in acquired transplantation tolerance. Although the cell interactions are undoubtedly complex, a discrete role can be identified for DC under well‐defined experimental conditions. Bone marrow‐derived DC progenitors (MHC class II+, B7–1dim, B7–2−) induce alloantigen‐specific hyporesponsiveness (anergy) in naive T cells in vitro. Moreover, costimulatory molecule‐deficient DC progenitors administered systemically prolong the survival of mouse heart or pancreatic islet allografts. How the regulation of donor DC phenotype and function relates to the balance between the immunogenicity and tolerogenicity of organ allografts remains to be determined. Copyright © 1995 AlphaMed Pres

A Branching Time Model of CSP

I present a branching time model of CSP that is finer than all other models of CSP proposed thus far. It is obtained by taking a semantic equivalence from the linear time - branching time spectrum, namely divergence-preserving coupled similarity, and showing that it is a congruence for the operators of CSP. This equivalence belongs to the bisimulation family of semantic equivalences, in the sense that on transition systems without internal actions it coincides with strong bisimilarity. Nevertheless, enough of the equational laws of CSP remain to obtain a complete axiomatisation for closed, recursion-free terms.Comment: Dedicated to Bill Roscoe, on the occasion of his 60th birthda

Stress dependent thermal pressurization of a fluid-saturated rock

Temperature increase in saturated porous materials under undrained conditions leads to thermal pressurization of the pore fluid due to the discrepancy between the thermal expansion coefficients of the pore fluid and of the solid matrix. This increase in the pore fluid pressure induces a reduction of the effective mean stress and can lead to shear failure or hydraulic fracturing. The equations governing the phenomenon of thermal pressurization are presented and this phenomenon is studied experimentally for a saturated granular rock in an undrained heating test under constant isotropic stress. Careful analysis of the effect of mechanical and thermal deformation of the drainage and pressure measurement system is performed and a correction of the measured pore pressure is introduced. The test results are modelled using a non-linear thermo-poro-elastic constitutive model of the granular rock with emphasis on the stress-dependent character of the rock compressibility. The effects of stress and temperature on thermal pressurization observed in the tests are correctly reproduced by the model

Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells

Donor liver-derived dendritic cells (DC) have recently been identified within various lymphoid and nonlymphoid tissues of organ allograft recipients, including nonimmunosuppressed mice transplanted with and permanently accepting major histocompatibility complex (MHC)-disparate hepatic allografts. These findings have raised questions about the basis of the tolerogenicity of the liver—and, in particular, about the properties of liver-derived DC. To study further the structure, immunophenotype and allostimu-latory activity of leukocytes resident in normal mouse (B10.BR; H-2k, I-Ek) liver, a procedure was developed to maximize the yield of viable, nonparenchymal cells (NPC) obtained following collagenase digestion of perfused liver fragments and density centrifugation (Per-coll). These cells comprised populations expressing lymphoid and myeloid cell surface antigens. As compared with spleen cells, they proved good allostimula-tors of naive (BIO; H-2b, I-E") splenic T cells when tested in primary mixed leukocyte reactions (MLR). After overnight (18-hr) incubation of the NPC, enrichment for transiently adherent, low-density (LD) cells on metrizamide gradients permitted the recovery of low numbers of cells (approx. 2-5 × 105 per liver), many of which displayed distinct DC morphology. Flow cytometric analysis revealed that these cells were CD3-, CD4-, CD8-, and B220-, but strongly expressed CD45 (leukocyte-common antigen), and mild-to-moderate levels of CD lib, heat-stable antigen, and CD44. The cells also expressed moderate intensity of NLDC 145 but not 33D1, DC restricted markers which have been shown to be differentially expressed on mouse DC isolated from various organs. This DC-enriched population was more strongly MHC class II(I-Ek)+ than NPC, as determined by immunocytochemistry and flow cytometry and exhibited much more potent allo-stimulatory activity for naive T cells. These findings demonstrate that freshly isolated murine liver NPC, and perhaps their counterparts in situ, exhibit allo-stimulatory activity that is enhanced in the nonadherent, low-density (DC-enriched) fraction after overnight culture. They further suggest that the © 1994 by Williams and Wilkins

Impact of ICARDA Research on Australian Agriculture

Research and Development/Tech Change/Emerging Technologies,