Major Histocompatibility Complex Restriction Between Hematopoietic Stem Cells and Stromal Cells In Vivo

Hashimoto, Futoshi; Sugiura, Kikuya; Inoue, Katsumi; Ikehara, Susumu

doi:10.1182/blood.v89.1.49

Cited by 104 publications

(21 citation statements)

References 22 publications

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“…17 We have found that IBM-BMT not only allows us to use low-dose irradiation as a pre-conditioning regimen 17 but also helps to suppress GVHD, 18 as this IBM-BMT method can efficiently recruit donor-derived stromal cells [including mesenchymal stem cells (MSCs)], which can support donor-derived haemopoietic stem cells. 1,[19][20][21] In addition, it has recently been shown, even in humans, that stromal cells or MSCs suppress GVHD. 22,23 The thymus is an organ in which T cells can be induced to differentiate from precursor T cells.…”

Section: Introductionmentioning

confidence: 99%

Adult thymus transplantation with allogeneic intra‐bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft‐versus‐host reaction and strong graft‐versus‐tumour effects

Miyake

Hosaka²,

Nishida³

et al. 2009

Immunology

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SummaryAlthough allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow-bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4 + FoxP3 + regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8 + T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR.

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Section: Introductionmentioning

confidence: 99%

Adult thymus transplantation with allogeneic intra‐bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft‐versus‐host reaction and strong graft‐versus‐tumour effects

Miyake

Hosaka²,

Nishida³

et al. 2009

Immunology

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“…Considering that syngeneic and allogeneic BMC coresided in common cellular clusters and adhesion appeared to improve BMC survival, it is possible that antigen disparity does not affect BMC interaction with stromal cells. Alternatively, deficient seeding of donor cells in recipient BM stroma could be restricted by antigenic barriers [10], as substantiated by inhibition of cobblestone formation in stromal cell cultures [11]. To elaborate on the characteristics and restrictions of donor BMC adhesion to recipient BM stroma, the seeding efficiency of syngeneic versus allogeneic lineage + BMC and lineage -HSPC was quantitatively assessed in situ.…”

Section: Introductionmentioning

confidence: 99%

Antigen Barriers or Available Space Do Not Restrict in Situ Adhesion of Hemopoietic Cells to Bone Marrow Stroma

Askenasy¹,

Farkas²

2002

STEM CELLS

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Israel, 14 Kaplan Street, Petach Tikva, 49202, Israel. Telephone: 9-723-925-3669; Fax: 9-723-925-3042; e-mail: anadir@012.net.il Received October 12, 2001; accepted for publication October 23, 2001. ©AlphaMed Press 1066-5099/2002 INTRODUCTIONThe early stages of bone marrow cell (BMC) engraftment include homing and seeding in recipient bone marrow (BM). Recent in vivo microscopy studies showed high traffic of homing BMC in recipient femur, which stopped when BMC seeded in stromal microenvironment [submitted manuscript]. If seeding is the dominant factor in determining the efficiency of homing, then adhesion should have the characteristics of the homing process. First, an approximately 16-fold higher homing efficiency of lineage -hemopoietic stem and progenitor

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“…Six months after BMT, the graft acceptance was examined, and the percentages of the donor cells in the peripheral blood were analyzed using a FACS. HSCs should show a better proliferative response than C3H HSCs, as we have previously shown [13]. It should be noted that all the pancreas allografts are accepted when more than 1% of allogeneic cells are detected in the PB of the recipients.…”

Section: Discussionmentioning

confidence: 81%

Long‐Term (>1 year) Analyses of Chimerism and Tolerance in Mixed Allogeneic Chimeric Mice Using Normal Mouse Combinations

et al. 2000

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We examined the induction of tolerance using pancreas allografts over the long term (>1 year) in mice for the human application of mixed allogeneic bone marrow transplantation (BMT). T cell-depleted BM cells (BMCs) of C57BL/6 (B6) and C3H/He (C3H) mice were transplanted at various ratios into lethally irradiated B6 mice. The percentages of C3H cells in the chimeric mice gradually decreased, finally declining to only a small percentage, except when the ratio of donor to recipient BMCs was 100:1. However, despite the marked decreases in C3H-type cells, all the pancreas allografts of C3H mice were accepted when more than 1% C3H cells were detected in the peripheral blood. To examine the relationships between percentages of transplanted donor cells and acceptance of pancreas allografts, various percentages of donor and recipient BMCs (5% to 30%) were transplanted. It was found that more than 10% donor cells were necessary for the pancreas allografts to be accepted. In vitro assays for mixed lymphocyte reaction and generation of cytotoxic T-lymphocytes revealed that spleen cells in chimeric mice accepting pancreas allografts are tolerant to both host-type and donortype major histocompatibility complex (MHC) determinants, but show a vigorous responsiveness to thirdparty MHC determinants. Since donor-type hemopoietic stem cells (HSCs) were detected in the BM and the liver of the chimeric mice, donor-derived HSCs and donor-derived hematolymphoid cells are responsible for the induction of tolerance. It should be noted that the percentage of donortype HSCs is higher in the liver (6.2%) than in the BM (0.9%).

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Major Histocompatibility Complex Restriction Between Hematopoietic Stem Cells and Stromal Cells In Vivo

Cited by 104 publications

References 22 publications

Adult thymus transplantation with allogeneic intra‐bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft‐versus‐host reaction and strong graft‐versus‐tumour effects

Adult thymus transplantation with allogeneic intra‐bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft‐versus‐host reaction and strong graft‐versus‐tumour effects

Antigen Barriers or Available Space Do Not Restrict in Situ Adhesion of Hemopoietic Cells to Bone Marrow Stroma

Long‐Term (>1 year) Analyses of Chimerism and Tolerance in Mixed Allogeneic Chimeric Mice Using Normal Mouse Combinations

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