Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts.

Slavin, Shimon; Reitz, Bruce A.; Bieber, Charles P.; Kaplan, Henry S.; Strober, Samuel

doi:10.1084/jem.147.3.700

Cited by 193 publications

(87 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The feasibility of induction of durable engraftment of stem cell allografts following nonmyeloablative conditioning is not new. Stable bone marrow engraftment following non-myeloablative conditioning with fractionated TLI alone [34][35][36][37][38] or one fraction of TLI 200 cGy and a single dose of cytoxan 39 led to induction of permanent and specific transplantation tolerance to all donor alloantigens, including skin allografts across strong MHC antigen barriers in mice and rats as has already been described by us [34][35][36][37][38][39] and confirmed by others. [40][41][42] Of 10 patients similarly treated with the non-myeloablative regimen, only 2 were mixed chimeras containing both donor and recipient cells, while 8 patients were already full donor chimeras one month following transplant.…”

Section: Discussionmentioning

confidence: 54%

Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen

Morecki

Gelfand

Nagler

et al. 2001

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

Summary:We have investigated the immune status of patients with hematologic malignancies treated with a low intensity conditioning in preparation for allogeneic stem cell transplantation. Conditioning consisted of fludarabine, anti-T lymphocyte globulin and low-dose busulfan, followed by infusion of allogeneic blood stem cells. This protocol resulted in rapid engraftment and complete replacement of host with donor hematopoietic cells. Immunological parameters of these patients were compared to those patients who were conditioned by an aggressive myeloablative regimen. Distribution of cell surface markers of lymphocyte subsets from both groups of patients was similar, but different from that of normal control cells. Reduced intensity or non-myeloablative conditioning prior to allogeneic stem cell transplantation (NST), hardly lowered the normal T cell-dependent mitogenic response even during the early period following transplant, while the myeloablative treatments resulted in a suppressed mitogenic reaction and in slow immune recovery. Reactivity of non-MHC restricted cytotoxic T cells was also at a normal level in patients who were treated with NST. We conclude that stem cell engraftment following reduced conditioning may result in early reconstitution of immune responses assessed in vitro. We hypothesize that clinical application of NST may lead to faster development of effective immune responses against residual host-type malignant and abnormal non-malignant hematopoietic cells, although the role of fludarabine on post-transplant infections remains to be investigated in a larger cohort of patients. Bone Marrow Transplantation (2001) 28, 243-249.

show abstract

Section: Discussionmentioning

confidence: 54%

Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen

Morecki

Gelfand

Nagler

et al. 2001

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

show abstract

“…The parabiotic animals were mixed chimeras, mimicking the effects of placental cross-circulation described by Owen in freemartin cattle (49), that included the acceptance of reciprocal skin grafts (50). The findings of Martinez, Shapiro, and Good (48) defined a principle that presaged the GVHD resistance of mixed chimerism in the total-lymphoid irradiation models of Slavin and Strober (51,52) and the experiments ofTIdstad and Sachs (53)(54)(55)(56). A more recent analogy to the archival parabiotic experiments has been provided by the mouse orthotopic hepatic transplant model of Qian et al (4) in which the liver allograft, which is spontaneously accepted with most strain combinations, has had the uncanny resemblance of a tolerogenic parabiotic partner to its chimeric and reciprocally tolerogenic recipient.…”

Section: Discussionmentioning

confidence: 99%

Variable Chimerism, Graft-Versus-Host Disease, and Tolerance After Different Kinds of Cell and Whole Organ Transplantation From Lewis to Brown Norway Rats

et al. 1995

View full text Add to dashboard Cite

“…We have studied the mechanism underlying transplantation tolerance induced by total lymphoid irradiation (TLI). In rodents (mice and rats) treated by TLI, tolerance to allogeneic skin grafts can be induced only if donor-type BM cells are also infused (5,6). Tolerance to perfused organ allografts can be induced in rats (6) and baboons (7) without concomitant infusion of marrow cells, suggesting that the organ itself may provide sufficient tolerogenic signals.…”

mentioning

confidence: 99%

Alloantigen persistence in induction and maintenance of transplantation tolerance.

Morecki¹,

Leshem²,

Eid³

et al. 1987

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

Infusion of parental bone marrow cells into F1 hybrids conditioned by total lymphoid irradiation (TLI) results in chimeras with a high percentage of donor-type cells, and without clinical signs of graft-vs.-host reaction. In these chimeras, a state of tolerance has been shown to be associated with paucity of cytotoxic T lymphocyte percursors (pCTL) reactive with host-type alloantigens. To determine whether the presence of tolerizing alloantigens is essential for maintenance of unresponsiveness, lymphohematopoietic cells obtained from such tolerant chimeras were transferred into supralethally irradiated recipients of two different genotypes: in one case the adoptive recipients were syngeneic with host-type cells, and in the other they were syngeneic with donor-type cells of the original chimeras, thus providing the chimeric cells with a tolerogen-free environment. After "parking" for 4 d in syngeneic donor-type mice, the transferred cells displayed a marked increase in the frequency of pCTL directed against tolerizing alloantigens, whereas a low pCTL frequency directed against the same H-2 target cells was maintained in allogeneic tolerizing-type adoptive recipients. Multiple injections of adoptive donor-type mice with tolerizing-type cells of the original chimera reestablished a low level of cytotoxic precursors. Cytotoxic activity against unrelated alloantigens was independent of the presence of tolerogen-presenting cells in the adoptively transferred mice. Our experimental model suggests that persistence of cells bearing tolerizing alloantigens is an essential requirement for maintenance of previously established tolerance.

show abstract

Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts.

Cited by 193 publications

References 9 publications

Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen

Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen

Variable Chimerism, Graft-Versus-Host Disease, and Tolerance After Different Kinds of Cell and Whole Organ Transplantation From Lewis to Brown Norway Rats

Alloantigen persistence in induction and maintenance of transplantation tolerance.

Contact Info

Product

Resources

About