scholarly journals Differential Effects of IL-2 and IL-6 on the Development of Three Distinct Precursor T-Cell Populations in the Thymus

1990 ◽  
Vol 1 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Naoko Nakano ◽  
Hitoshi Kikutani ◽  
Tadamitsu Kishimoto
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Cell Populations ◽  
High Dose ◽  
Transfer System ◽  
Cell Sorter ◽  
Lineage Markers ◽  
Low Levels ◽  
Normal Differentiation

Three distinct T-cell precursors: bone marrow cells that express low levels of the Thy-1 antigen but no lineage markers (Thy-1-lo/BM); CD4-, CD8-, and CD3-thymocytes that express low levels of the Thy-1 antigen (Thy-1-lo/Thym); and CD4-, CD8-, and CD3-thymocytes that express high levels of the Thy-1 antigen and the IL-2 Rαchain (Thy-1+/ IL2R+) were isolated by fluorescence-activated cell sorter (FACS). These three populations expanded with different kinetics in the thymus of irradiated recipient mice after intrathymic transfer. When a high dose of human recombinant IL-2 (r-IL-2) or human recombinant IL-6 (r-IL-6) was administered, r-IL-6 accelerated donor Thy-1+/IL2R+to differentiate, whereas r-IL-2 blocked normal differentiation and expansion of donor Thy-1-lo/Thym, but did not show any significant effect on donor Thy-1+/IL2R+. Neither r-IL-2 nor r-IL-6 worked directly on donor Thy-1-lo/BM in this transfer system.

scholarly journals Tpre, a new alloantigen encoded in the IgT-C region of chromosome 12, is expressed on bone marrow of nude mice, fetal T cell hybrids, and fetal thymus.

1983 ◽  
Vol 157 (2) ◽  
pp. 419-432 ◽  
Author(s):  
F L Owen
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Precursor Cell ◽  
Chromosome 12 ◽  
Cell Populations ◽  
Fetal Thymus ◽  
Cell Hybrids ◽  
T Cell Antigens ◽  
Adult Thymus

A new T cell alloantigen, Tpre, has been identified by monoclonal F.6.9.1 antibody. This antigen is encoded by a gene linked to the cluster of T cell antigens in the IgT-C region of chromosome 12 (Tthy, Tind, and Tsu). Tpre is distinct from Tthy, Tind, or Tsu because it is expressed on bone marrow cells of the AKR nustr/nustr, the thymus repopulating precursor cell in normal adult marrow, and normal fetal thymocytes. Several fetal and adult T cell hybrids express these antigens independently. Tpre and Tthy are expressed on largely overlapping cell populations in adult thymus.

scholarly journals Clonal deletion of postthymic T cells: veto cells kill precursor cytotoxic T lymphocytes.

1992 ◽  
Vol 175 (3) ◽  
pp. 863-868 ◽  
Author(s):  
K Hiruma ◽  
H Nakamura ◽  
P A Henkart ◽  
R E Gress
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
High Dose ◽  
Spleen Cells ◽  
Clonal Deletion ◽  
Veto Cells ◽  
Veto Cell ◽  
Marrow Cells ◽  
Ctl Responses

Veto cell-mediated suppression of cytotoxic T lymphocyte (CTL) responses has been proposed as one mechanism by which self-tolerance is maintained in mature T cell populations. We have previously reported that murine bone marrow cells cultured in the presence of high-dose interleukin 2 (IL-2) (activated bone marrow cells [ABM]) mediate strong veto suppressor function. To examine mechanisms by which ABM may suppress precursor CTL (p-CTL) responses, we used p-CTL generated from spleen cells of transgenic mice expressing a T cell receptor specific for H-2 Ld. It was demonstrated that the cytotoxic response by these p-CTL after stimulation with irradiated H-2d/k spleen cells was suppressed by DBA/2 (H-2d) ABM, but not by B10.BR (H-2k) ABM or dm1 (Dd, Ld mutant) ABM. Flow cytometry analysis with propidium iodide staining revealed that these p-CTL were specifically deleted by incubation with H-2d ABM, but not with H-2k ABM. These data indicate that ABM veto cells kill p-CTL with specificity for antigens expressed on the surface of the ABM, and that the mechanism for veto cell activity of ABM is clonal deletion of p-CTL.

scholarly journals Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus.

1988 ◽  
Vol 167 (5) ◽  
pp. 1671-1683 ◽  
Author(s):  
G J Spangrude ◽  
C E Muller-Sieburg ◽  
S Heimfeld ◽  
I L Weissman
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Cell Lineage ◽  
Mouse Bone Marrow ◽  
Surface Markers ◽  
Facs Analysis ◽  
Colony Forming Units ◽  
Low Levels ◽  
Intrathymic Injection

Two-color FACS analysis of mouse bone marrow reveals a rare population, comprising 0.1-0.3% of the total, that expresses low levels of the Thy-1 antigen but does not express any of five surface markers that characterize differentiated hematolymphoid cells. We demonstrate here that this fraction of mouse bone marrow is enormously enriched in cells that can home to the thymus and differentiate into mature T lymphocytes, subsequently migrating to peripheral lymphoid organs. Only a subset of the FACS-isolated fraction (1/90 after intrathymic injection) is capable of responding to the thymic microenvironment with a productive commitment to the T cell lineage. A second fraction of mouse bone marrow, which expresses how levels of Thy-1 but is also positive for at least one of five hematolymphoid lineage-specific markers, also contains cells that home to the thymus and establish colonies of thymocytes. The two fractions each contribute approximately equal amounts of thymic colony-forming units (CFUt) to the bone marrow, and together can account for at least half of the CFUt in whole bone marrow.

Mouse CD11c+ B220+ Gr1+plasmacytoid dendritic cells develop independently of the T-cell lineage

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2852-2857 ◽  
Author(s):  
Isabel Ferrero ◽  
Werner Held ◽  
Anne Wilson ◽  
Fabienne Tacchini-Cottier ◽  
Freddy Radtke ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Bone Marrow Cells ◽  
T Cell Development ◽  
Cell Lineage ◽  
Notch 1 ◽  
T Cell Factor ◽  
Plasmacytoid Dcs ◽  
Lineage Markers ◽  
Mixed Chimeras

The developmental origin of dendritic cells (DCs) is controversial. In the mouse CD8α+ and CD8α− DC subsets are often considered to be of lymphoid and myeloid origin respectively, although evidence on this point is conflicting. Very recently a novel CD11c+ B220+ DC subset has been identified that appears to be the murine counterpart to interferon alpha (IFNα)–producing human plasmacytoid DCs (PDCs). We show here that CD11c+ B220+ mouse PDCs, like human PDCs, are present in the thymus and express T lineage markers such as CD8α and CD4. However, the intrathymic development of PDCs can be completely dissociated from immature T lineage cells in mixed chimeras established with bone marrow cells from mice deficient for either Notch-1 or T-cell factor 1, two independent mutations that severely block early T-cell development. Our data indicate that thymic PDCs do not arise from a bipotential T/DC precursor.

Effects of 200cH medications on mice bone marrow cells and macrophages

2021 ◽  
Vol 10 (35) ◽  
pp. 75-76
Author(s):  
Carolina De Oliveira ◽  
Ana Paula R. Abud ◽  
Eneida Da Lozzo ◽  
Raffaello Di Bernardi ◽  
Simone De Oliveira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Cells ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Hematopoietic Lineage ◽  
Lineage Markers ◽  
Lachesis Muta ◽  
Nonadherent Cells ◽  
Marrow Cells

Paracelsus once wrote: "All things are poison and nothing is without poison, only the dose permits something not to be poisonous." Latter Hahnemann formulated the law of similars, preparations which cause certain symptoms in healthy individuals if given in diluted form to patients exhibiting similar symptoms will cure it. Highly diluted natural complexes prepared according to Hahnemann’s ancient techniques may represent a new form of immunomodulatory therapy. The lack of scientific research with highly diluted products led us to investigate the in vivo and in vitro actions of commonly used medications. Here we describe the results of experimental studies aimed at verifying the effects of Mercurius solubilis, Atropa Belladonna, Lachesis muta and Bryonia alba. All medications were at 200cH dilution. Animals were maintained for 7 days and were allowed to drink the medications, which were prepared in a way that the final dilution and agitation (200cH) was performed in drinking water. The medication bottle was changed and sucussed every afternoon. Co-culture of non treated mice bone marrow cells and in vitro treated peritoneal macrophages were also performed. After animal treatment the bone marrow cells were immunophenotyped with hematopoietic lineage markers on a flow cytometer. We have determined CD11b levels on bone marrow cells after culture and co-culture with treated macrophages and these macrophages were processed to scanning electron microscopy. We have observed by morphological changes that macrophages were activated after all treatments. Mercurius solubilis treated mice showed an increase in CD3 expression and in CD11b on nonadherent bone marrow cells after co-culture with in vitro treatment. Atropa Belladonna increased CD45R and decreased Ly-6G expression on bone marrow cells after animal treatment. Lachesis muta increased CD3, CD45R and, CD11c expression and decreased CD11b ex vivo and in nonadherent cells from co-culture. Bryonia alba increased Ly-6G, CD11c and CD11b expression ex vivo and when in co-culture CD11b was increased in adherent cells as well as decreased in nonadherent cells. With these results we have demonstrated that highly diluted medications act on immune cells activating macrophages, and changing the expression profile of hematopoietic lineage markers. Highly diluted medications are less toxic and cheaper than other commonly used medications and based on our observations, it is therefore conceivable that this medications which are able to act on bone marrow and immune cells may have a potential therapeutic use in clinical applications in diseases were the immune system is affected and also as regenerative medicine as it may allow proliferation and differentiation of progenitor cells.

scholarly journals Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells

1999 ◽  
Vol 190 (9) ◽  
pp. 1257-1262 ◽  
Author(s):  
Chiyu Wang ◽  
Molly A. Bogue ◽  
Jonathan M. Levitt ◽  
David B. Roth
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Bone Marrow Cells ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Immunodeficient Mice ◽  
Thymocyte Differentiation ◽  
Marrow Cells

In SCID (severe combined immunodeficient) mice, proper assembly of immunoglobulin and T cell receptor (TCR) genes is blocked by defective V(D)J recombination so that B and T lymphocyte differentiation is arrested at an early precursor stage. Treating the mice with gamma irradiation rescues V(D)J rearrangement at multiple TCR loci, promotes limited thymocyte differentiation, and induces thymic lymphomas. These effects are not observed in the B cell lineage. Current models postulate that irradiation affects intrathymic T cell precursors. Surprisingly, we found that transfer of irradiated SCID bone marrow cells to unirradiated host animals rescues both TCR rearrangements and thymocyte differentiation. These data indicate that irradiation affects precursor cells at an earlier stage of differentiation than was previously thought and suggest new models for the mechanism of irradiation rescue.

scholarly journals Myelosuppressive conditioning is required to achieve engraftment of pluripotent stem cells contained in moderate doses of syngeneic bone marrow

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 939-948 ◽  
Author(s):  
Y Tomita ◽  
DH Sachs ◽  
M Sykes
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Whole Body ◽  
Mixed Chimerism ◽  
Hematopoietic Stem ◽  
Donor Cells ◽  
Donor Type ◽  
Low Levels

Abstract We have investigated the requirement for whole body irradiation (WBI) to achieve engraftment of syngeneic pluripotent hematopoietic stem cells (HSCs). Recipient B6 (H-2b; Ly-5.2) mice received various doses of WBI (0 to 3.0 Gy) and were reconstituted with 1.5 x 10(7) T-cell-depleted (TCD) bone marrow cells (BMCs) from congenic Ly-5.1 donors. Using anti-Ly-5.1 and anti-Ly-5.2 monoclonal antibodies and flow cytometry, the origins of lymphoid and myeloid cells reconstituting the animals were observed over time. Chimerism was at least initially detectable in all groups. However, between 1.5 and 3 Gy WBI was the minimum irradiation dose required to permit induction of long-term (at least 30 weeks), multilineage mixed chimerism in 100% of recipient mice. In these mice, stable reconstitution with approximately 70% to 90% donor-type lymphocytes, granulocytes, and monocytes was observed, suggesting that pluripotent HSC engraftment was achieved. About 50% of animals conditioned with 1.5 Gy WBI showed evidence for donor pluripotent HSC engraftment. Although low levels of chimerism were detected in untreated and 0.5-Gy-irradiated recipients in the early post-BM transplantation (BMT) period, donor cells disappeared completely by 12 to 20 weeks post-BMT. BM colony assays and adoptive transfers into secondary lethally irradiated recipients confirmed the absence of donor progenitors and HSCs, respectively, in the marrow of animals originally conditioned with only 0.5 Gy WBI. These results suggest that syngeneic pluripotent HSCs cannot readily engraft unless host HSCs sustain a significant level of injury, as is induced by 1.5 to 3.0 Gy WBI. We also attempted to determine the duration of the permissive period for syngeneic marrow engraftment in animals conditioned with 3 Gy WBI. Stable multilineage chimerism was uniformly established in 3-Gy-irradiated Ly-5.2 mice only when Ly-5.1 BMC were injected within 7 days of irradiation, suggesting that repair of damaged host stem cells or loss of factors stimulating engraftment may prevent syngeneic marrow engraftment after day 7.

Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.

1998 ◽  
Vol 16 (1) ◽  
pp. 165-172 ◽  
Author(s):  
C Hesdorffer ◽  
J Ayello ◽  
M Ward ◽  
A Kaubisch ◽  
L Vahdat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Multiple Drug Resistance ◽  
Autologous Bone Marrow Transplantation ◽  
High Dose Chemotherapy ◽  
Multiple Drug ◽  
High Dose ◽  
Hematopoietic Stem

PURPOSE Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy. PATIENTS AND METHODS Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy. RESULTS High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered. CONCLUSION These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.

scholarly journals Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer.

1987 ◽  
Vol 166 (1) ◽  
pp. 219-234 ◽  
Author(s):  
P W Kantoff ◽  
A P Gillio ◽  
J R McLachlin ◽  
C Bordignon ◽  
M A Eglitis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Gene Transfer ◽  
Adenosine Deaminase ◽  
Nonhuman Primates ◽  
Bone Marrow Cells ◽  
Hematopoietic Cells ◽  
Retroviral Vector ◽  
Infected Cells ◽  
Low Levels ◽  
Neomycin Resistance

Primate bone marrow cells were infected with a retroviral vector carrying the genes for human adenosine deaminase (h-ADA) and bacterial neomycin resistance (neor). The infected cells were infused back into the lethally irradiated donor animals. Several monkeys fully reconstituted and were shown to express the h-ADA and neor genes at low levels in their recirculating hematopoietic cells for short periods of time.

scholarly journals Reutilization of Thymidine in Various Groups of Rat Bone Marrow Cells

Blood ◽  
1971 ◽  
Vol 37 (3) ◽  
pp. 340-348 ◽  
Author(s):  
H. J. HEINIGER ◽  
L. E. FEINENDEGEN ◽  
K. BüRKI
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Single Cells ◽  
Marrow Cell ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Salvage Pathway ◽  
Blast Cells ◽  
Autoradiographic Technique ◽  
Rat Bone

Abstract Thymidine reutilization was studied in single cells of the rat bone marrow. Using 3H-TdR in parallel with 125I-UdR in conjunction with the autoradiographic technique, cells of the erythrocytic series, the megakaryocytic group, and the lymphoid cells were analyzed. Reutilization of thymidine was observed only in those cells known to synthesize DNA. An estimate of the amounts of the thymidine reutilized by the salvage pathway indicated that approximately 40-60 per cent of the thymidine in the blast cells is supplied from DNA of dead cells. This value is similar to that reported previously for whole bone marrow cell populations, suggesting the presence of a common thymidine pool within the bone marrow.

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