scholarly journals Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 491-496 ◽  
Author(s):  
A Bacigalupo ◽  
M Podesta ◽  
MC Mingari ◽  
L Moretta ◽  
G Piaggio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Suppressor Activity ◽  
Healthy Donors ◽  
Marrow Cells

Abstract T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

scholarly journals Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 491-496
Author(s):  
A Bacigalupo ◽  
M Podesta ◽  
MC Mingari ◽  
L Moretta ◽  
G Piaggio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Suppressor Activity ◽  
Healthy Donors ◽  
Marrow Cells

T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

Intra–bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3292-3299 ◽  
Author(s):  
Taketoshi Kushida ◽  
Muneo Inaba ◽  
Hiroko Hisha ◽  
Naoya Ichioka ◽  
Takashi Esumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Autoimmune Diseases ◽  
Bone Marrow Cells ◽  
Donor Cell ◽  
Allogeneic Bone ◽  
Early Recovery ◽  
New Strategy ◽  
Marrow Cells

Abstract Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy × 2, followed by intra–bone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy × 2 + IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donor-derived hemopoietic progenitor cells concomitantly increased. Furthermore, donor-derived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy × 2 + IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (Thy1.2+/B220+/CD4−/CD8−) disappeared. Hematolymphoid cells were reconstituted with donor-derived cells, and newly developed T cells were tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex determinants. Successful cooperation was achieved among T cells, B cells, and antigen-presenting cells when evaluated by in vitro antisheep red blood cell responses. These findings clearly indicate that this new strategy (IBM-BMT) creates the appropriate hemopoietic environment for the early recovery of hemopoiesis and donor cell engraftment, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants. This strategy would therefore be suitable for human therapy.

scholarly journals Cell-mediated amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 479-483
Author(s):  
T Nagasawa ◽  
T Sakurai ◽  
H Kashiwagi ◽  
T Abe
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bone Marrow ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Culture System ◽  
Bone Marrow Cells ◽  
Rare Complication ◽  
Systemic Lupus ◽  
Marrow Cells

We studied a patient with a rare complication of amegakaryocytic thrombocytopenia (AMT) associated with systemic lupus erythematosus (SLE). To investigate the underlying pathogenesis of AMT, the effects of peripheral blood T cells and serum on human megakaryocyte progenitor cells were studied using in vitro coculture techniques. Mononuclear bone marrow cells (2 X 10(5) from normal donors produced 33.6 +/- 8.8 (n = 10) colony-forming unit-megakaryocytes (CFU-M) in our plasma clot system. When 2 X 10(5) of the patient's T cells were added to the culture system, the number of CFU-M decreased to only 3.5 +/- 0.6/2 X 10(5) bone marrow cells. No evidence of inhibitory effects was found by the addition of the patient's serum and complement to the culture system. The T cells stored at -80 degrees C on admission were also capable of suppressing autologous CFU-M after recovery from AMT. These results indicate that in vitro suppression of CFU-M from allogenic and autologous bone marrow cells by this patient's T cells provides an explanation for the pathogenesis of AMT associated with SLE.

scholarly journals Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1997-2004 ◽  
Author(s):  
A Srivastava ◽  
E Bruno ◽  
R Briddell ◽  
R Cooper ◽  
C Srivastava ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Replication ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Parvovirus B19 ◽  
Northern Analysis ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Marrow Cells

Abstract Parvovirus B19 infection leads to transient aplastic crises in individuals with chronic hemolytic anemias or immunodeficiency states. An additional unexplained sequela of B19 infection is thrombocytopenia. Because B19 is known to have a remarkable tropism for human erythropoietic elements, and is not known to replicate in nonerythroid cells, the etiology of this thrombocytopenia is uncertain. We sought to define the pathobiology of B19-associated thrombocytopenia by examining the role of B19 on in vitro megakaryocytopoiesis. B19 infection of normal human bone marrow cells significantly suppressed megakaryocyte (MK) colony formation compared with mock-infected cells. No such inhibition was observed with a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell interaction was also studied at the molecular level. Whereas low-density bone marrow cells containing erythroid precursor cells supported B19 DNA replication, no viral DNA replication was observed in B19-infected MK-enriched fractions as determined by the presence of viral DNA replicative intermediates on Southern blots. However, analysis of total cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level expression of the B19 genome as detected by quantitative RNA dot blots as well as by Northern analysis. Furthermore, a frame-shift mutation in a recombinant AAV-B19 hybrid genome segment that encodes the viral nonstructural (NS1) protein significantly reduced the observed inhibition of MK colony formation. These studies indicate tissue- tropism of B19 beyond the erythroid progenitor cell, and lend support to the hypothesis that B19 genome expression may be toxic to cell populations that are nonpermissive for viral DNA replication.

scholarly journals Generation of CFU-C suppressor T cells in vitro. III. Failure of mitogen-primed T cells from patients with chronic granulocytic leukemia to inhibit the growth of normal CFU-C

Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1447-1452 ◽  
Author(s):  
F Frassoni ◽  
A Bacigalupo ◽  
M Podesta ◽  
MT Van Lint ◽  
G Piaggio ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Colony Formation ◽  
Chronic Phase ◽  
Pokeweed Mitogen ◽  
Suppressor Activity ◽  
Chronic Granulocytic Leukemia ◽  
Granulocytic Leukemia ◽  
Marrow Cells

Abstract T lymphocytes were derived by E rosetting from the peripheral blood (PB) and bone marrow (BM) of 15 patients with chronic granulocytic leukemia (CGL) in the chronic phase of their disease. T cells were also obtained from 12 healthy individuals. T cells were incubated overnight either in culture medium (RPMI) or RPMI plus pokeweed mitogen (PWM). The supernatants were then recovered and the cells washed in fresh RPMI. T cells from normal donors and from CGL patients were then cocultured with normal allogeneic marrow cells grown in soft agar for CFU-C colony formation. Target marrow cells were also grown in agar in the presence of T-derived supernatants. The results of this study can be summarized as follows. (1) Normal PB and BM T cells efficiently suppressed autologous and allogeneic CFU-C growth after PWM stimulation. (2) T cells derived from peripheral blood or marrow of CGL patients failed to inhibit CFU-C growth, whether pretreated with PWM or not. (3) The supernatants of PWM-treated normal T cells strongly inhibited CFU-C colony formation, whereas the supernatants of PWM- treated CGL T cells had no CFU-C/suppressor activity. These data indicate that T cells from CGL patients cannot be primed to become CFU- C suppressor cells after PWM: stimulation in vitro and cannot release a soluble inhibitor of granulopoiesis produced by PWM-primed normal T cells.

Granulocyte-macrophage colony formation in vitro using human non-phagocytic bone marrow cells

1988 ◽  
Vol 188 (6) ◽  
pp. 405-409 ◽  
Author(s):  
N. Ohhara ◽  
S. Okamura ◽  
S. Hayashi ◽  
T. Otsuka ◽  
Y. Niho
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Macrophage Colony ◽  
Marrow Cells

scholarly journals Long-lasting skin allograft tolerance in adult mice induced across fully allogeneic (multimajor H-2 plus multiminor histocompatibility) antigen barriers by a tolerance-inducing method using cyclophosphamide.

1989 ◽  
Vol 169 (1) ◽  
pp. 213-238 ◽  
Author(s):  
H Mayumi ◽  
R A Good
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Cells ◽  
Effector T Cells ◽  
Mixed Chimerism ◽  
Allogeneic Bone ◽  
Spleen Cells ◽  
Skin Allograft ◽  
Cell Injection ◽  
Marrow Cells

A new method of cyclophosphamide (CP)-induced skin allograft tolerance in mice that can regularly overcome fully allogeneic (major H-2 plus non-H-2) antigen barriers in mice has been established. The components of the method are intravenous or intraperitoneal administration of 50-100 micrograms of anti-Thy-1.2 mAb on day -1, intravenous injection of 90 x 10(6) allogeneic spleen cells mixed with 30 x 10(6) allogeneic bone marrow cells from the same donor on day 0, and intraperitoneal injection of 200 mg/kg CP on day 2. In each of four fully allogeneic donor----recipient combinations, including C3H/HeJ (C3H; H-2k)----C57BL/6J(B6; H-2b), B6----C3H, BALB/cByJ (BALB; H-2d)----B6, and BALB----C3H, long-lasting survival of skin allografts was induced in most of the recipient mice. The specific tolerant state induced was dependent on the doses of the antibody and bone marrow cells used. The optimal timing of CP treatment to induce tolerance was found to be 1-3 d after the stimulating cell injection. Treatment with the anti-Thy-1.2 antibody together with CP on day 2 after the cell injection on day 0 also induced profound tolerance. In the B6 mice made tolerant of C3H with antibody, C3H spleen cells plus C3H bone marrow cells, and then CP, a minimal degree of stable mixed chimerism was established and the antitolerogen (C3H) immune responses examined here, including delayed footpad reaction (DFR), CTL activity, and capacity for antibody production against donor-strain antigens were abrogated in a tolerogen-specific manner. From cell transfer experiments, the mechanism of tolerance could be largely attributed to reduction of effector T cells reactive against the tolerogen, and strong suppressive influences that might prolong skin allograft survival directly were not detected in the tolerant mice. Moreover, pretreatment with anti-Thy-1.2 antibody or anti-L3T4 (CD4) antibody was more effective than pretreatment with anti-Lyt-1 (CD5) antibody or anti-Lyt-2 (CD8) antibody as an initial step in tolerance induction. These results suggest that permanent tolerance to fully allogeneic skin grafts may be induced because antibody given before the stimulating cell injection reduces the number of reactive T cells in the recipient mice. This antibody treatment may facilitate an antigen-stimulated destruction of responding and thus proliferating cells with CP by preventing a possibly less proliferative, more rapid maturation of reactive T cells or by destroying residual effector T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Human donor bone marrow cells induce in vitro “suppressor T cells” that functionally suppress autologous B cells

2003 ◽  
Vol 64 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Manuel R Carreno ◽  
Laphalle Fuller ◽  
James M Mathew ◽  
Gaetano Ciancio ◽  
George W Burke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Bone Marrow Cells ◽  
Suppressor T Cells ◽  
Human Donor ◽  
Donor Bone Marrow ◽  
Marrow Cells

scholarly journals Inhibition of human macrophage colony formation by interleukin 4.

1989 ◽  
Vol 170 (2) ◽  
pp. 577-582 ◽  
Author(s):  
J H Jansen ◽  
G J Wientjens ◽  
W E Fibbe ◽  
R Willemze ◽  
H C Kluin-Nelemans
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Direct Action ◽  
Colony Growth ◽  
Interleukin 4 ◽  
Human Macrophage ◽  
Macrophage Colony ◽  
Marrow Cells

We investigated the effects of human rIL-4 on in vitro hematopoiesis. A profound inhibition of macrophage colony formation by IL-4 was observed, whereas colony growth of other lineages was not affected. Inhibition of macrophage colony growth was not restricted to GM-CSF-induced colony growth but was also present in cultures stimulated with M-CSF. This inhibition was not only observed in cultures of light density bone marrow cells, but also in cultures of monocyte- and T lymphocyte-depleted bone marrow cells. Since a similar inhibition was observed in cultures of CD34+HLA-DR+-enriched bone marrow cells, a direct action of IL-4 on monocyte-committed progenitor cells is suggested.

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