scholarly journals Immunoregulatory effects of allogeneic mixed chimerism induced by nonmyeloablative bone marrow transplantation on chronic inflammatory arthritis and autoimmunity in interleukin-1 receptor antagonist–deficient mice

2006 ◽  
Vol 54 (6) ◽  
pp. 1878-1887 ◽  
Author(s):  
Seok Goo Cho ◽  
So-Youn Min ◽  
Min Jung Park ◽  
Kyung Wha Lee ◽  
Young-Gyu Cho ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Receptor Antagonist ◽  
Marrow Transplantation ◽  
Inflammatory Arthritis ◽  
Interleukin 1 ◽  
Mixed Chimerism ◽  
Chronic Inflammatory Arthritis ◽  
Interleukin 1 Receptor Antagonist ◽  
Deficient Mice

Immunoregulatory Effects of Allogeneic Mixed Chimerism Induced by T-Cell Depleted, Nonmyeloablative Bone Marrow Transplantation on Chronic Inflammatory Arthritis and Autoimmunity Developed in Interleukin-1 Receptor Antagonist-Deficient Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1277-1277
Author(s):  
Seok-Goo Cho ◽  
Min-Chung Park ◽  
So-Youn Min ◽  
Young-Gyu Cho ◽  
Seok Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Inflammatory Arthritis ◽  
Interleukin 1 ◽  
Mixed Chimerism ◽  
Control Groups ◽  
Chronic Inflammatory Arthritis

Abstract Objective: To investigate the immunoregulatory effects of allogeneic mixed chimerism induced by T-cell depleted, nonmyeloablative bone marrow transplantation (TCD-NMT) on chronic inflammatory arthritis and autoimmunity developed in interleukin-1 receptor antagonist-deficient (IL-1Ra−/ −) mice. Methods: IL-1Ra−/ − mice (H-2kd) were treated with anti-asialoGM1 Ab, TBI 500 cGy, and TCD-NMT from C57BL/6 mice (H-2kb). Engraftment and chimerism were evaluated on peripheral blood (PB), lymph node, and spleen by multi-color flow cytometry. The severity of arthritis was evaluated by clinical score and histopathology. IgG1 and IgG2a subtype of anti-type II collagen (CII) were measured in PB samples. After T cells were stimulated with CII, ovalbumin, and phytohemagglutinin, T-cell proliferation response and cytokines production (INF-g, TNF-a, IL-10, and IL-17) in culture supernatant were assayed. Results: All the transplanted IL-1Ra mice showed marked improvement of arthritis within 3 weeks after transplantation as well as successful induction of mixed chimerism. Mice in mixed chimerism showed higher level of anti-CII IgG1 and lower level of anti-CII IgG2a and weaker T cell proliferative response than in control groups, such as no-treatment and conditioning only without BM rescue. In mixed chimera, INF-g, TNF-a and IL-17 production from CII-stimulated T cells was significantly suppressed and IL-10 production was significantly increased as compared to the control groups. Conclusion: These observations indicate that the introduction of allogeneic mixed chimerism has a strong immunoregulatroy potential to correct established chronic inflammatory arthritis and autoimmunity originating from dysregulated proinflammatory cytokine network.

ENDOGENOUS INTERLEUKIN 1 RECEPTOR ANTAGONIST DURING HUMAN BONE MARROW TRANSPLANTATION

1997 ◽  
Vol 63 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Hubert Schwaighofer ◽  
Georg Oberhuber ◽  
Holger Hebart ◽  
Hermann Einsele ◽  
Manfred Herold ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Receptor Antagonist ◽  
Marrow Transplantation ◽  
Interleukin 1 ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Interleukin 1 Receptor Antagonist

scholarly journals Bone Marrow Transplantation in Apolipoprotein E–Deficient Mice

1997 ◽  
Vol 17 (11) ◽  
pp. 3117-3126 ◽  
Author(s):  
Miranda Van Eck ◽  
Nicole Herijgers ◽  
John Yates ◽  
Nigel J. Pearce ◽  
Peter M. Hoogerbrugge ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Apolipoprotein E ◽  
Marrow Transplantation ◽  
Deficient Mice

scholarly journals Role of interleukin-25 in development of spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice

2017 ◽  
Vol 12 ◽  
pp. 62-65
Author(s):  
Yasuharu Abe ◽  
Aya Nambu ◽  
Sachiko Yamaguchi ◽  
Ayako Takamori ◽  
Hajime Suto ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Interleukin 1 Receptor Antagonist ◽  
Interleukin 25 ◽  
Deficient Mice

scholarly journals Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 296-304 ◽  
Author(s):  
DC Roy ◽  
R Tantravahi ◽  
C Murray ◽  
K Dear ◽  
B Gorgone ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Natural History ◽  
Marrow Transplantation ◽  
Cytogenetic Analysis ◽  
Common Finding ◽  
Mixed Chimerism ◽  
Allogeneic Bone ◽  
Donor Cells ◽  
History Of

Mixed hematopoietic chimerism (MC) is a common finding after allogeneic bone marrow transplantation (BMT), but the natural history of this phenomenon remains unclear. To understand the evolution and the implications of this finding, we performed a prospective analysis of the development of mixed chimerism in 43 patients with hematologic malignancies who received bone marrow (BM) from human leukocyte antigen (HLA)-identical sibling donors. T-cell depletion in vitro with anti-T12 (CD6) monoclonal antibody and rabbit complement was used as the only method of graft-versus-host disease (GVHD) prophylaxis. Overall, MC was identified in peripheral blood (PB) and BM in 22 of 43 (51%) patients evaluated. MC was found by restriction fragment length polymorphism (RFLP) analysis in 21 of 40 (53%) patients, by cytogenetic analysis in 6 of 29 (21%) patients, and by red blood cell phenotyping in 4 of 9 (44%) patients. RFLP studies were performed at 0.5, 1, 3, 6, 9, and 12 months post-BMT and then every 6 months, and showed a high probability of developing MC in the first 6 months after BMT followed by stabilization after 12 months. Cytogenetic analysis was less sensitive in detecting MC. Once MC was detected after BMT, the percentage of recipient cells increased very slowly over more than 3 years of follow- up, and no patient reverted to complete donor hematopoiesis (CDH). Thus, recipient and donor cells remained in a relative state of equilibrium for prolonged periods that seemed to favor recipient cells over donor cells. Patient's disease, remission status, or intensity of the transplant preparative regimen did not influence the subsequent development of mixed chimerism. Early immunologic reconstitution was the only factor that correlated with the subsequent chimeric status of the patients. The percentage and absolute number of T3 (CD3) and T4 (CD4) positive cells at day 14 after BMT were significantly higher in the patients who maintained CDH but NK cell reconstitution was similar in both groups, suggesting that early reconstitution with T cells may play a role in preventing recovery of recipient cells after BMT. GVHD was also associated with maintenance of CDH, but the probability of relapse, survival, and disease-free survival was identical in patients with MC and CDH.

scholarly journals Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Bin Chen ◽  
Tatsuo Kawai ◽  
Thomas R. Spitzer
Keyword(s):  
Bone Marrow ◽  
Kidney Transplantation ◽  
Bone Marrow Transplantation ◽  
Organ Transplantation ◽  
Marrow Transplantation ◽  
Mixed Chimerism ◽  
Clonal Deletion ◽  
Primate Model ◽  
Hematopoietic Chimerism ◽  
Specific Tolerance

The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable.

scholarly journals Mixed chimerism after bone marrow transplantation and the risk of relapse [letter]

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4385-4386 ◽  
Author(s):  
E Roux ◽  
C Helg ◽  
B Chapius ◽  
M Jeannet ◽  
E Roosnek
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Mixed Chimerism ◽  
Risk Of Relapse

Coexistence of Two Functioning T-Cell Repertoires in Healthy Ex-Thalassemics Bearing a Persistent Mixed Chimerism Years After Bone Marrow Transplantation

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3432-3438 ◽  
Author(s):  
Manuela Battaglia ◽  
Marco Andreani ◽  
Marisa Manna ◽  
Sonia Nesci ◽  
Paola Tonucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Mixed Chimerism ◽  
Functional Studies ◽  
Repertoire Analysis ◽  
Donor Cells ◽  
Donor Lymphocytes

Bone marrow transplantation (BMT) from an HLA-identical donor is an established therapy to cure homozygous β-thalassemia. Approximately 10% of thalassemic patients developed a persistent mixed chimerism (PMC) after BMT characterized by stable coexistence of host and donor cells in all hematopoietic compartments. Interestingly, in the erythrocytic lineage, close to normal levels of hemoglobin can be observed in the absence of complete donor engraftment. In the lymphocytic lineage, the striking feature is the coexistence of immune cells. This implies a state of tolerance or anergy, raising the issue of immunocompetence of the host. To understand the state of the T cells in PMC, repertoire analysis and functional studies were performed on cells from 3 ex-thalassemics. Repertoire analysis showed a profound skewing. This was due to an expansion of some T cells and not to a collapse of the repertoire, because phytohemagglutinin stimulation showed the presence of a complex repertoire. The immunocompetence of the chimeric immune systems was further established by showing responses to alloantigens and recall antigens in vitro. Both host and donor lymphocytes were observed in the cultures. These data suggest that the expanded T cells play a role in specific tolerance while allowing a normal immune status in these patients.

Sign in / Sign up

Export Citation Format

Share Document