Minor Histocompatibility Antigens on Canine Hemopoietic Progenitor Cells

Weber, Martin; Lange, Claudia; Günther, W.; Franz, Monika; Kremmer, Elisabeth; Kolb, Hans‐Jochem

doi:10.4049/jimmunol.170.12.5861

Cited by 23 publications

(17 citation statements)

References 59 publications

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“…Using this criterion, we demonstrate that LPS-stimulated MoDC in contrast to MΦ up-regulated MHC II, CD80 and CD40, similar to observations found with other species [3, 8, 33] upon stimulation with ligands to TLR2, -3 and -7 MoDC reacted with a significant up regulation of MHC II and CD86 as seen in other species [27, 34, 42]. The lack of responsiveness to TLR9 ligand CpG could be related to observations also found for humans and pigs, which describe that only plasmacytoid DC express this receptor [34, 40]. Future studies are required with more CpG sequences and the canine plasmacytoid DC need to be identified before any conclusion can be drawn.…”

Section: Discussionsupporting

confidence: 84%

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells

Gutzwiller

Moulin²,

Zurbriggen

et al. 2010

Vet. Res.

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Dendritic cells (DC) represent a heterogeneous cell family of major importance for innate immune responses against pathogens and antigen presentation during infection, cancer, allergy and autoimmunity. The aim of the present study was to characterize canine DC generated in vitro with respect to their phenotype, responsiveness to toll-like receptor (TLR) ligands and T-cell stimulatory capacity. DC were derived from monocytes (MoDC) and from bone marrow hematopoietic cells cultured with either Flt3-ligand (FL-BMDC) or with GM-CSF (GM-BMDC). All three methods generated cells with typical DC morphology that expressed CD1c, CD11c and CD14, similar to macrophages. However, CD40 was only found on DC, CD206 on MΦ and BMDC, but not on monocytes and MoDC. CD1c was not found on monocytes but on all in vitro differentiated cells. FL-BMDC and GM-BMDC were partially positive for CD4 and CD8. CD45RA was expressed on a subset of FL-BMDC but not on MoDC and GM-BMDC. MoDC and FL-DC responded well to TLR ligands including poly-IC (TLR2), Pam3Cys (TLR3), LPS (TLR4) and imiquimod (TLR7) by up-regulating MHC II and CD86. The generated DC and MΦ showed a stimulatory capacity for lymphocytes, which increased upon maturation with LPS. Taken together, our results are the basis for further characterization of canine DC subsets with respect to their role in inflammation and immune responses.

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Section: Discussionsupporting

confidence: 84%

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells

Gutzwiller

Moulin²,

Zurbriggen

et al. 2010

Vet. Res.

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“…15,16 GVHD can also target recipient hematopoietic stem cells. [17][18][19][20][21] However, none of the patients in this report had evidence of immune-mediated hemolysis despite the presence of ABO incompatibilities in 6 of the 8 patients. Moreover, none of the patients had evidence of GVHD, and it is therefore very unlikely that selective depletion of maturing recipient RBCs was caused by alloimmune responses directed against these cells.…”

Section: Discussionmentioning

confidence: 99%

Evidence for ineffective erythropoiesis in severe sickle cell disease

Krishnamurti

Kutok

et al. 2005

Blood

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IntroductionSickle cell disease (SCD) is a common and severe disorder in which a missense mutation in the ␤-globin gene results in polymerization of hemoglobin S under deoxygenating conditions, leading to chronic peripheral hemolysis and intravascular vaso-occlusion. Less fully appreciated is the extent to which sickle hemoglobin in committed erythroid precursor cells might also affect earlier events in erythropoiesis. Improved understanding of the impact of SCD on intramedullary erythropoiesis is relevant to the development of new therapeutic strategies for this chronic debilitating disease.One approach to directly assess the contribution of ineffective erythropoiesis to the pathophysiology of sickle cell disease is to analyze erythropoiesis in sickle cell disease patients who have undergone matched related donor allogeneic stem cell transplantation (SCT) following a nonmyeloablative (NMA) conditioning regimen. A variety of nonmyeloablative conditioning regimens have been developed to facilitate engraftment of donor stem cells and reduce the treatment-related toxicity of hematopoietic SCT. [1][2][3][4] In this nonmyeloablative setting, host hematopoiesis frequently persists following transplantation and coexists with engrafted donor cells within the marrow. Depending on the underlying disease and the intensity of the conditioning regimen, stable mixed hematopoietic chimerism occurs frequently and can persist for long intervals. Mixed hematopoietic chimerism has been well documented after allogeneic hematopoietic SCT for SCD, and this provides a unique opportunity to perform a direct side-by-side comparison of normal and sickle erythropoiesis in vivo. 5,6 To distinguish between donor and host erythropoiesis, we previously developed methods to specifically measure erythroid lineage chimerism in both nucleated and non-nucleated erythroid elements. Although molecular methods for measurement of donor chimerism are well established, they are based on analysis of genomic DNA, and thus measure nucleated-cell chimerism, which is predominantly leukocyte derived in peripheral blood. 7-9 Therefore, in addition to measuring overall engraftment by analysis of genomic DNA, the present studies also use two alternate methods to distinguish between donor and host-derived erythropoiesis. One method relies on direct enumeration of donor-derived erythroid precursors on paraffin-imbedded marrow sections following staining with a donor-specific marker, such as red blood cell (RBC) isohemagglutinin antigens in an ABO disparate setting. A second method uses a novel molecular assay, RNA ␤-globin pyrosequencing, which directly measures erythroid lineage-specific chimerism from total RNA by quantifying the amount of RBC-specific RNA transcripts that bear a donor or host-specific single nucleotide polymorphism (SNP) or mutation. 6 In addition to using the sickle mutation as an informative ␤-globin SNP, we also previously identified an alternate ␤-globin SNP, 3H3, that occurs at high minor allele frequency. 6 Since ␤-globin RNA is expressed...

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“…In another experiment, the responsiveness of the cells to hematopoietic growth factors was tested. Cells harvested from day 6 of coculture proliferated in response to a mixture of hematopoietic growth factors known to support the growth of canine hematopoietic progenitor cells [12], whereas much less proliferation was observed with cells harvested from day 0 of coculture (data not shown). Importantly, our in vitro differentiation results were obtained using cells at passages 10 -12.…”

mentioning

confidence: 94%

Canine Embryo‐Derived Stem Cells—Toward Clinically Relevant Animal Models for Evaluating Efficacy and Safety of Cell Therapies

Schneider¹,

Adler²,

Braun

et al. 2007

STEM CELLS

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Pluripotent embryonic stem (ES) cells, which are available in mouse [1,2] and human [3], are permanent cell lines that can differentiate into cell types of all three germ layers. Therefore, ES cells have a remarkable potential for both basic research and clinical applications toward replacement of degenerated or malignant cells. From the perspective of hematology, where stem cell therapies are most advanced, ES cells have a number of advantages over conventional sources of transplantable material. They can be expanded indefinitely in vitro, and, more importantly, they can be obtained from a bank representing major haplotype combinations [4] or may even be derived by reprogramming somatic cells from individual patients. Proof of principle for this "therapeutic cloning" concept has been provided in the mouse [5]; however, translation of ES cell-based therapeutic strategies to clinical application requires larger animal models for predictive efficacy and safety studies.The dog has been used for preclinical studies of stem cell transplantation, and many techniques have been derived from canine studies [6]. Furthermore, techniques applicable to canine cells and dogs can be applied to man, taking into account known biologic properties of the dog [7]. Since the dog is the ideal preclinical model for testing new therapies for many human diseases, the availability of canine embryo-derived stem cells for in vitro differentiation studies will be of great value for the development of new therapies, especially in hematology. Moreover, nuclear transfer from canine somatic cells is possible [8], providing the opportunity to evaluate the concept of "therapeutic cloning" in a clinically relevant animal model.In a recent report, Hatoya and colleagues [9] describe the isolation of two ES-like cell lines from canine blastocysts. The cell lines were shown to exhibit characteristic ES-like morphology and expression of pluripotency markers. Importantly, the cells formed embryoid bodies in suspension culture, which differentiated upon adhesive culture into various cell types, including neuron-like, epithelium-like, fibroblast-like, melanocyte-like, and myocardium-like cells, demonstrating that these cells are indeed pluripotent. Unfortunately, it was not possible to maintain the undifferentiated phenotype of the cell lines beyond passage 8.We have performed similar studies that confirm the possibility of establishing canine embryo-derived cell lines and, more importantly, demonstrate for the first time that these cells can be

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Minor Histocompatibility Antigens on Canine Hemopoietic Progenitor Cells

Cited by 23 publications

References 59 publications

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells

Evidence for ineffective erythropoiesis in severe sickle cell disease

Canine Embryo‐Derived Stem Cells—Toward Clinically Relevant Animal Models for Evaluating Efficacy and Safety of Cell Therapies

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