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At least 19 recordsLinked to original sources
PubMed1980

Karyotype analysis of leukocytes of gray collie (cyclic neutropenia)-normal bone marrow transplant chimeras six years after transplantation.

Karyotype analysis was made on the leukocytes of 2 gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras transplanted 6 years previously to correct cyclic neutropenia of the gray Collie syndrome. In a male-to-female transplant chimera, all of the to metaphase spreads showed the karyotype of male donor origin. In this and the male-to-male chimera, the morphology of all chromosomes examined showed no gross anomalies or breaks which might be of recipient origin.

Agranulocytosis↗
PubMed1986

[A study on the location of synthetic sites of the fourth and fifth components of the complement system in allogeneic bone marrow chimeras and hepatocyte transplantation chimeras].

In this study, the tissue sites for synthesis of fourth and fifth components of complement (C4, C5) have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. One group of chimeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice which produced high level of C4 into irradiated recipients which were characterized by having low level of C4 or vice versa. The results showed that C4 or C5 antigens were present in the sera of the chimeras only when recipients were strains which were characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 and C5 in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimeric mice. However, when hepatocytes isolated from the C5-sufficient strain were inoculated into the spleens of C5-deficient bone marrow chimeras, detectable amounts of C5 were present in the sera. These results indicate that C5 protein is synthesized and delivered to the blood in vivo by liver cells.

Animals↗
PubMed1992

Histopathological changes in exocrine glands of murine transplantation chimeras. I: The development of Sjögren's syndrome-like changes secondary to GVH induced lupus syndrome.

Sjögren's syndrome (SS) is a connective tissue disease characterized by general affection of exocrine glands. The three main components of SS are: dry eyes, dry mouth, and other connective tissue disease. When only two of these, dry eyes and dry mouth, are present, the disease is designated primary SS. In the presence of the third component, most commonly SLE or RA, with one or both of the two first components the disease is designated secondary SS. In murine transplantation chimeras, we have demonstrated the development of both primary and secondary SS depending upon the mouse strains used. We transferred large numbers of viable leucocytes from homozygotic donors to heterozygotic recipients. When DBA/2 mice were used as donors, a full-developed SLE-syndrome, with autoantibodies against native DNA, nuclear antigens, and red blood cells was observed. We found immune deposits in skin ("lupus band") and kidneys, immune complex glomerulonephritis (ICGN), proteinuria, ascites, and hepatosplenomegaly. In later stages, we found a generalized dacryoadenitis. In the kidneys we found interstitial nephritis, and occasionally "half-moon" nephritis. In skin, immune deposits were demonstrated in intercellular spaces. These findings are similar to those found in patients with Sjögren's syndrome secondary to SLE. The murine transplantation chimera is therefore an experimental model for spontaneous autoimmune diseases.

Animals↗
PubMed1994

Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues.

Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I-dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

Animals↗
PubMed1989

The mechanism of graft-host-tolerance in murine radiation chimeras transplanted across minor histocompatibility barriers.

A better understanding of the mechanism(s) involved in graft-host-tolerance following allogeneic bone marrow transplantation is needed to develop new strategies to prevent graft-versus-host disease (GVHD). Based on previous studies, mainly in MHC-mismatched donor-recipient pairs, three hypotheses have been proposed: clonal deletion, active suppression and lack of adequate antigen-presenting cells. Our goal was to identify the mechanism(s) by which tolerance is achieved and maintained in radiation chimeras transplanted across minor histocompatibility barriers. Healthy (B6----LP) chimeras were obtained following injection of 10(7) C57BL/6 marrow cells to irradiated (9.5 Gy) LP hosts and used experimentally 100 days after chimerization. The tolerance state of (B6----LP) chimeras could not be abrogated after i.v. transfer of 5 x 10(7) donor-type spleen cells alone or with repeated i.p. injection of host-type antigen-presenting cells. No GVHD was observed when 10(7) marrow cells plus 5 x 10(7) spleen cells from (B6----LP) chimeras were injected to irradiated LP recipients. Chimera spleen cells suppressed GVHD when adoptively transferred to LP recipients of a C57BL/6 graft. These results suggest that in this model the presence of suppressor cells is both necessary and sufficient to maintain graft-host-tolerance.

Animals↗
PubMed1985

Assessment of immunocompetence by limiting dilution analysis in long-term T cell depletion chimeras transplanted across the MHC barrier.

Chimeras were generated in a system in which donor C57BL/6 bone marrow plus spleen cells were T-cell-depleted prior to transplantation into lethally irradiated DBA/2 recipients. This protocol permits donor lymphohematopoietic engraftment and protects transplanted mice from development of lethal GVHD. The frequencies of alloantigen-specific cytotoxic T cells (CTL) and/or CTL precursors (CTL-P) in the chimera spleens were determined by limiting dilution analysis. This identified a small population of host-reactive CTL-P. The presence of host-reactive CTL-P in the absence of detectable anti-host immune response raises questions concerning the maintenance of the tolerant state in chimeras. Using mixtures of chimera and normal C57BL/6 splenocytes we found no evidence by limiting-dilution analysis for regulatory cells capable of dampening antihost immune reactivity in chimera spleens. We next measured the frequency of third-party-reactive CTL-P in chimeras. Chimeras displayed low CTL-P frequency by the 30th day posttransplant, which increased 15-21-fold over a five-month interval. Interestingly, both chimeric and irradiated syngeneic reconstituted control mice recovered anti-third-party CTL-P at a similar rate, but CTL-P levels never reached those measured in normal unirradiated control mice, suggesting that the radiation regimen has a long-lasting influence on host immunocompetence. In concomitant experiments we measured third-party CTL generation in MLC. Our findings suggest that measurement of CTL generation in MLC may be a less sensitive assessment of immunocompetence than LDA analysis. Our data also suggest that irradiated T-cell-depleted chimeras may suffer prolonged immunologic deficiencies based on reduced frequencies of alloreactive CTL-P.

Animals↗
PubMed1992

Histopathological changes in exocrine glands of murine transplantation chimeras. II: Sjögren's syndrome-like exocrinopathy in mice without lupus nephritis. A model of primary Sjögren's syndrome.

Autoimmune reactions are evoked in hybrid mice after induction of a chronic graft-versus-host reaction by transfer of viable leucocytes from one of the parental strains to non-irradiated F1 recipients. We have previously demonstrated an SLE-like syndrome early in the reaction, with an additional Sjögren's syndrome-like glandular affection occurring later. In this study, we used Balb/c mice as donors and Balb/cxCBA/H-T6 F1 hybrids as recipients. We found serum autoantibodies characteristic of SLE after 9 weeks but not after 20 weeks. No clinical signs of disease were seen at any time. After prolonged studies (5 months), we found heavy inflammation in Harderian, salivary, and tear glands. All animals survived the entire length of the experiment without signs of renal failure. The pathological manifestations: lymphocytic infiltration of exocrine glands, and enlargement of lymph nodes, are similar to those seen in patients with Sjögren's syndrome. This murine transplantation chimera may be a useful experimental model for primary Sjögren's syndrome.

Animals↗
PubMed1997

Role of in situ IL-2r and TGF-beta expression in tolerant vascularized bone marrow (limb) transplant chimeras.

We hypothesized that an increase in IL-2 activated T cells in situ within the marrow component of a transplanted limb may adversely affect development of tolerance, while increased TGF-beta expression locally would facilitate tolerance induction and/or maintenance. Digital image analysis of cellular expression of IL-2r in the bone marrow was significantly increased in the CON and TXP limbs for both GVHD and tolerant recipients as compared to normal limb marrow (P < .02). The amount of cellular expression of TGF-beta was significantly increased in the GVHD animals, both CON and TXP, as compared to the tolerant animals (43.2 +/- 3.1 vs 10.6 +/- 2.6; P < .000001). Our results show that increased IL-2r and TGF-beta expression in situ within the bone marrow is an important effect common to both alloimmune tolerance and GVHD induction with VBMT chimeras. The dramatic increase in the expression of TGF-beta in the GVHD transplanted limbs may explain the profound immunosuppression that results. Additionally, moderate expression of TGF-beta in situ in tolerant chimeras may represent a mechanism for the induction and maintenance of tolerance.

Animals↗
PubMed2003

Migration of adult myogenic precursor cells as revealed by GFP/nLacZ labelling of mouse transplantation chimeras.

We studied the migratory behaviour of adult muscle precursor cells in the mouse into and from skeletal muscle grafts using green fluorescent protein (GFP) and nuclear LacZ transgenes as complementary and double markers of the cell's origin. Owing to the small molecular mass and extreme solubility of GFP, this label provided a drastically increased sensitivity for detection compared with the markers that had been used previously. During the first six weeks after the operation, the graft/host border was well defined, with only occasional local intermingling and co-fusion of host and donor myogenic cells. Seven to eleven weeks after the operation we found that the host myogenic cells had migrated into the graft, and graft myogenic cells had migrated into the adjacent host muscle, with integration of donor nuclei into pre-existing myotubes or muscle fibres. There was no indication of an origin of, or target for, these myogenic cells besides neighbouring muscles. Our observations indicate migration of these cells through solid muscle tissue, over a distance of several millimetres. The migratory activity of adult myogenic precursor cells can be stimulated by traumatic events in either the target muscle or the muscle of origin.

Animals↗
PubMed1998

Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests primarily on recipient-derived CD8 T cells.

Cytomegalovirus (CMV) infection during the transient immunodeficiency after bone marrow transplantation (BMT) develops into disease unless antiviral CD8 T cells are restored in due course. Histoincompatibility between donor and recipient is associated with increased risk. Complications may include a rejection response against the foreign major histocompatibility complex (MHC) antigens and a lack of antiviral control resulting from a misfit between donor-derived T cells and the antigenic viral peptides presented in recipient tissues. Here we have established a murine model of CMV disease after experimental BMT performed across a single MHC class I disparity. Specifically, BALB/c bone marrow cells expressing the prevailing antigen-presenting molecule Ld were transplanted into the Ld gene deletion mutant BALB/c-H-2(dm2), an experimental setting that entails a selective risk of host-versus-graft but not graft-versus-host response. The reconstituted T-cell population proved to be chimeric in that it consisted of Ld-positive donor-derived and Ld-negative recipient-derived cells. Pulmonary infiltrates did not include cytolytic T cells directed against Ld. This finding implies that the infection did not trigger a host-versus-graft response. Notably, upon adoptive transfer, donor-derived CD8 T cells preferentially protected tissues of donor genotype, whereas recipient-derived CD8 T cells protected tissues of either genotype. We infer from these data that the focus on immunodominant antigens presented by Ld within the donor cell population distracted the donor T cells from protecting recipient tissues and that protection in the chimeras was therefore primarily based on recipient T cells. As a consequence, T-cell chimerism after BMT should give a positive prognosis with respect to control of CMV.

Animals↗
PubMed1991

Specification of neurepithelium and surface epithelium in avian transplantation chimeras.

Previous studies of the avian blastoderm have revealed that extensive displacements occur within the epiblast during gastrulation and neurulation. The present study had two main purposes: (1) to map the origin and movement of prospective surface epithelial cells, and (2) to ask whether neurepithelial and surface epithelial cell fates are determined prior to cell movement, or whether they arise later as a result of the ultimate position attained by cells through their movement. Our results show that the rostral and lateral intraembryonic and extraembryonic surface epithelium originates as far laterally as at the area pellucida-area opaca interface of the early epiblast. Intraembryonic surface epithelial cells rearrange relative to one another, extending medially to contribute to the formation of the neural folds, whereas extraembryonic surface epithelial cells maintain their lateral positions, spreading uniformly as the epiblast expands. Our results further show that surface epithelial and neurepithelial cell fates are labile at the onset of neurulation, suggesting that cell fate is specified following cell movement.

Animals↗
PubMed2000

Transplantation of gene-modified human bone marrow stromal cells into mouse-human bone chimeras.

Transplantation of BM stromal cells engineered to secrete therapeutic factors could represent a treatment for a large array of hematologic disorders. The aim of this study was to evaluate the susceptibility of human BM stromal cell precursors to retroviral gene transfer, then the ability of those to be transplanted in vivo. We have transduced a recombinant retrovirus encoding the mouse CD2 antigen into STRO-1+ cells selected from adult and fetal BM. Gene-modified stromal cells were injected intravenously into NOD-SCID mice engrafted previously with pieces of human fetal hematopoietic bone. Using nested PCR, transgenic human cells were detected both in the marrow of human bone grafts and in the BM, liver, and spleen of host mice 7 weeks after grafting. These data indicate that BM stromal progenitor cells are targets for retrovirus-mediated gene transfer and can home to hematopoietic tissues on engraftment through the bloodstream of nonconditioned hosts.

Adult↗