Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations.
Summary of "Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations."
Tangnararatchakit K, Tirapanich W, Anurathapan U, Tapaneya-Olarn W, Pakakasama S, Jootar S, Slavin S, Hongeng S. Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations. Abstract: The present case report represents a successful attempt to induce transplantation tolerance to organ allograft by combined administration of donor hematopoietic cells and kidney based on in vivo deletion of alloreactive host-vs-graft and graft-vs-host alloreactive T cells following non-myeloablative conditioning. We were able to induce mixed and eventually full donor chimerism and tolerance of kidney allograft in a 15-yr-old male with ESRD after cisplatin treatment and autologous HSCT for mediastinal germ cell tumor. Our approach to induce tolerance was based on preferential depletion of alloreactive T cells induced by exposure to donor's alloantigens and administration of cyclophosphamide at day 2 and day 3 after stem cell infusion. Additional non-specific immunosuppression as part of the conditioning included exposure to two fractions of TLI, treatment with alemtuzumab (monoclonal anti-CD52) and short-term conventional IS treatment to avoid early graft loss, because of request of IRB. Using this approach, with rapid tapering of all conventional IS treatment, the patient maintains good renal functions without evidence of both acute and chronic rejection for 32 months off all medications.
Affiliation
Departments of Pediatrics Surgery Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand International Center for Cell Therapy & Cancer Immunotherapy (CTCI), Weizman Center, Tel Aviv, Israel.
Journal Details
This article was published in the following journal.
Name: Pediatric transplantation
ISSN: 1399-3046
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22553996
- DOI: http://dx.doi.org/10.1111/j.1399-3046.2012.01701.x
Medical and Biotech [MESH] Definitions
Transplantation Chimera
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
Hemangioblasts
Bipotential angio-hematopoietic stem cells that give rise to both HEMATOPOIETIC STEM CELLS and ENDOTHELIAL CELLS.
Growth Differentiation Factor 15
A growth differentiation factor that is secreted in response to cell stress and in response to MACROPHAGE ACTIVATION. In addition growth differentiation factor 15 demonstrates a diverse array of biological properties including the induction of cartilage formation, the inhibition of hematopoietic progenitor proliferation, and the induction of neuronal migration.
Graft Enhancement, Immunologic
The induction of prolonged survival and growth of allografts of either tumors or normal tissues which would ordinarily be rejected. It may be induced passively by introducing graft-specific antibodies from previously immunized donors, which bind to the graft's surface antigens, masking them from recognition by T-cells; or actively by prior immunization of the recipient with graft antigens which evoke specific antibodies and form antigen-antibody complexes which bind to the antigen receptor sites of the T-cells and block their cytotoxic activity.
Dendritic Cells
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
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