Allogeneic Hematopoietic Stem Cell Transplantation in Recipients of Cellular or Solid Organ Allografts

Kenyon, Norma S.; Chatzipetrou, Maria; Tzakis, Andreas G.; Miller, Joshua; Alejandro, Rodolfo; Ricordi, Camillo

doi:10.1007/978-1-4615-4987-1_6

Cited by 2 publications

(3 citation statements)

References 104 publications

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“…Alternatively, their MLR-suppressing activity and Th2-like IL-4 production may contribute to protecting developing B cells from potentially autoreactive Th1 cells in the BM microenvironment. In either case, these results, in conjunction with previous murine and human data (13,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), indicate that BM-derived CD1d-reactive T cells may regulate GvHD in allogeneic BM transplantation and contribute to allograft tolerance. Therapeutic expansion of such cells in the setting of hemopoietic cell transplantation may provide a means to suppress GvHD, which complements the potential graft-vs-tumor activity of other NK T cells (15,16,33,36).…”

Section: Cd1d-reactive Bm-derived T Cells Specifically Suppress Mlrsupporting

confidence: 75%

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Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses

Exley¹,

Tahir²,

Cheng³

et al. 2001

The Journal of Immunology

144

143

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Murine bone marrow (BM) NK T cells can suppress graft-vs-host disease, transplant rejection, and MLRs. Human BM contains T cells with similar potential. Human BM was enriched for NK T cells, ∼50% of which recognized the nonpolymorphic CD1d molecule. In contrast to the well-characterized blood-derived CD1d-reactive invariant NK T cells, the majority of human BM CD1d-reactive T cells used diverse TCR. Healthy donor invariant NK T cells rapidly produce large amounts of IL-4 and IFN-γ and can influence Th1/Th2 decision-making. Healthy donor BM CD1d-reactive T cells were Th2-biased and suppressed MLR and, unlike the former, responded preferentially to CD1d+ lymphoid cells. These results identify a novel population of human T cells which may contribute to B cell development and/or maintain Th2 bias against autoimmune T cell responses against new B cell Ag receptors. Distinct CD1d-reactive T cell populations have the potential to suppress graft-vs-host disease and stimulate antitumor responses.

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Section: Cd1d-reactive Bm-derived T Cells Specifically Suppress Mlrsupporting

confidence: 75%

“…Human BM similarly contains cells that can suppress MLR (25,26) and GvHD and induce tolerance to allografts (27)(28)(29)(30)(31). We report in this work that human BM was highly enriched for CD161 ϩ noninvariant CD1d-reactive T cells.…”

mentioning

confidence: 75%

Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses

Exley¹,

Tahir²,

Cheng³

et al. 2001

The Journal of Immunology

144

143

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“…In this group, we examined the effect of intraportal codelivery of islets and DBMCs on POD 0, followed by intravenous infusions of DBMCs on PODs 4 or 5 and 11. The timing of DBMC infusion was based on previous clinical studies, in which delayed marrow infusion was found to be optimal in the setting of solid organ or islet transplantation (35). Group 2 had eight animals that received the same induction therapy with thymoglobulin and fludarabine.…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

et al. 2010

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OBJECTIVETo test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model of islet/bone marrow transplantation.RESEARCH DESIGN AND METHODSCynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, and karyotype. Allogeneic donor MSCs were cotransplanted intraportally with islets on postoperative day (POD) 0 and intravenously with donor marrow on PODs 5 and 11. Recipients were followed for stabilization of blood glucose levels, reduction of exogenous insulin requirement (EIR), C-peptide levels, changes in peripheral blood T regulatory cells, and chimerism. Destabilization of glycemia and increases in EIR were used as signs of rejection; additional intravenous MSCs were administered to test the effect on reversal of rejection.RESULTSMSC phenotype and a normal karyotype were observed through passage 11. IL-6, IL-10, vascular endothelial growth factor, TGF-β, hepatocyte growth factor, and galectin-1 gene expression levels varied among donors. MSC treatment significantly enhanced islet engraftment and function at 1 month posttransplant (n = 8), as compared with animals that received islets without MSCs (n = 3). Additional infusions of donor or third-party MSCs resulted in reversal of rejection episodes and prolongation of islet function in two animals. Stable islet allograft function was associated with increased numbers of regulatory T-cells in peripheral blood.CONCLUSIONSMSCs may provide an important approach for enhancement of islet engraftment, thereby decreasing the numbers of islets needed to achieve insulin independence. Furthermore, MSCs may serve as a new, safe, and effective antirejection therapy.

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Allogeneic Hematopoietic Stem Cell Transplantation in Recipients of Cellular or Solid Organ Allografts

Cited by 2 publications

References 104 publications

Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses

Cutting Edge: A Major Fraction of Human Bone Marrow Lymphocytes Are Th2-Like CD1d-Reactive T Cells That Can Suppress Mixed Lymphocyte Responses

Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

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