scholarly journals CELLS INVOLVED IN THE IMMUNE RESPONSE

1969 ◽  
Vol 129 (4) ◽  
pp. 757-774 ◽  
Author(s):  
Nabih I. Abdou ◽  
Maxwell Richter
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow ◽  
Red Cells ◽  
Allogeneic Bone ◽  
Sheep Red Blood Cells ◽  
Sheep Red Cells

Irradiated rabbits given allogeneic bone marrow cells from normal adult donors responded to an injection of sheep red blood cells by forming circulating antibodies. Their spleen cells were also capable of forming many plaques using the hemolysis in gel technique, and were also capable of undergoing blastogenesis and mitosis and of incorporating tritiated thymidine upon exposure to the specific antigen in vitro. However, irradiated rabbits injected with allogeneic bone marrow obtained from rabbits injected with sheep red blood cells 24 hr prior to sacrifice (primed donors) were incapable of mounting an immune response after stimulation with sheep red cells. This loss of reactivity by the bone marrow from primed donors is specific for the antigen injected, since the immune response of the irradiated recipients to a non-cross-reacting antigen, the horse red blood cell, is unimpaired. Treatment of the bone marrow donors with high-titered specific antiserum to sheep red cells for 24 hr prior to sacrifice did not result in any diminished ability of their bone marrow cells to transfer antibody-forming capacity to sheep red blood cells. The significance of these results, with respect to the origin of the antigen-reactive and antibody-forming cells in the rabbit, is discussed.

scholarly journals Constitutive Expression of a CD44 Variant Isoform on T Cells Facilitates Regaining of Immunocompetence in Allogeneic Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 873-885 ◽  
Author(s):  
Margot Zöller ◽  
Annette Schmidt ◽  
Angela Denzel ◽  
Jürgen Moll
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
Constitutive Expression ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Cd44 Variant

Abstract Constitutive expression of a rat CD44 variant isoform, rCD44v4-v7, on murine T cells accelerates immune responsiveness. Because prolonged immunodeficiency can be a major drawback in allogeneic bone marrow transplantation, we considered it of special interest to see whether repopulation of lethally irradiated syngeneic and allogeneic mice may be influenced by constitutive expression of the rCD44v4-v7 transgene. When lethally irradiated syngeneic and allogeneic mice were reconstituted with bone marrow cells (BMC) from rCD44v4-v7 transgenic (TG) or nontransgenic (NTG) mice, the former had a clear repopulation advantage: thymocytes expanded earlier after reconstitution and, as a consequence, higher numbers of lymphocytes were recovered from spleen and lymph nodes. Lymphocytes also displayed functional activity in advance to those from mice reconstituted with BMC from NTG mice. Most importantly, after the transfer of BMC from TG mice into an allogeneic host, the frequency of host-reactive T cells decreased rapidly. Apparently, this was due to accelerated induction of tolerance. Because these effects were counterregulated by an rCD44v6-specific antibody, it is likely that they could be attributed to the rCD44v4-v7 TG product. Thus, expression of a CD44 variant isoform at high levels facilitated reconstitution with allogeneic BMC by accelerated establishment of tolerance and the regaining of immunocompetence.

scholarly journals CELLS INVOLVED IN THE IMMUNE RESPONSE

1969 ◽  
Vol 130 (1) ◽  
pp. 165-184 ◽  
Author(s):  
Nabih I. Abdou ◽  
Maxwell Richter
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Human Serum Albumin ◽  
Antibody Formation ◽  
Gamma Globulin ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Neonatal Administration

Rabbits were made immunologically tolerant to either human serum albumin or bovine gamma globulin by the neonatal administration of antigen. At 10 wk of age, they were challenged with the tolerogenic antigen and found to be non-responsive. However, these tolerant rabbits could respond with humoral antibody formation directed toward the tolerogenic antigen if they were treated with normal, allogeneic bone marrow or bone marrow obtained from a rabbit made tolerant toward a different antigen. They were incapable of responding if they were given bone marrow obtained from a rabbit previously made tolerant to the tolerogenic antigen. Irradiated rabbits were unable to respond if treated with tolerant bone marrow, but could respond well if given normal bone marrow. Since it has previously been demonstrated that the antibody-forming cell, in an irradiated recipient of allogeneic bone marrow, is of recipient and not donor origin, the data presented strongly indicate that the unresponsive cell in the immunologically tolerant rabbit is the antigen-reactive cell.

A novel application of cyclosporine A in nonmyeloablative pretransplant host conditioning for allogeneic BMT

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1166-1172 ◽  
Author(s):  
Boris Nikolic ◽  
Guiling Zhao ◽  
Kirsten Swenson ◽  
Megan Sykes
Keyword(s):  
Bone Marrow ◽  
Cyclosporine A ◽  
Bone Marrow Cells ◽  
Corticosteroid Treatment ◽  
Marrow Transplant ◽  
Allogeneic Bone Marrow ◽  
Whole Body ◽  
Allogeneic Bone ◽  
Central Tolerance ◽  
Bone Marrow Engraftment

The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on day −5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI) on day 0, allows fully major-histocompatibility-complex–mismatched allogeneic bone marrow engraftment and the induction of immunologic tolerance. TI is required in this model to overcome alloreactivity and possibly to make “space” in the recipient thymus so that lasting central tolerance can be achieved. In addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and glucocorticoids have a powerful influence on the thymus. In this study, we evaluated whether the administration of CYA to recipient mice for 12 days prior to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a combination of both, could create space and overcome alloresistance in the thymus by specifically depleting immature and mature thymocytes prior to BMT. High levels of multilineage donor hematopoietic repopulation and specific transplantation tolerance were achieved in mice treated from days −15 to −3 with CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day −5, followed by 3 Gy WBI and 15 × 106 allogeneic bone marrow cells on day 0. Vβ analysis suggested a central deletional tolerance mechanism. The same treatment without CYA pretreatment allowed only transient chimerism, without tolerance. Corticosteroid treatment abolished the engraftment-promoting and tolerance-inducing effects of CYA. These results demonstrate a novel pretransplantation-only application of CYA, which facilitates allogeneic marrow engraftment with minimal conditioning, by creating thymic space and/or overcoming intrathymic alloresistance.

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