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(PDF) Kidney Rejection in Chimeric Bone Marrow and Renal Transplants
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{"work":{"id":124810405,"created_at":"2024-10-17T08:01:26.630-07:00","from_world_paper_id":260250961,"updated_at":"2024-11-28T01:08:22.074-08:00","_data":{"publisher":"Elsevier BV","ai_title_tag":"Kidney Rejection in Chimeric Bone Marrow and Renal Transplants","grobid_abstract":"Although there is evidence linking hematopoietic chimerism-induction and solid organ transplant tolerance, the mechanistic requirements for chimerism-induced tolerance are not clearly elucidated. To address this, we used an MHC-defined primate model to determine the impact of impermanent, T cell-poor, mixed-chimerism on renal allograft survival. We compared two cohorts: one receiving a bone marrow + renal transplant (\"BMT/renal\") and one receiving only a renal transplant. Both cohorts received maintenance immunosuppression with CD28/CD40directed costimulation blockade and sirolimus. As previously demonstrated, this transplant strategy consistently induced compartmentalized donor chimerism, (significant whole-blood chimerism, lacking T cell chimerism). This chimerism was not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival time (MST, 76 days) was not significantly different than the renal transplant alone MST (85 days, p= 0. 46), with histopathology documenting T-cell mediated rejection. Flow cytometric analysis revealed significant enrichment for CD28-/CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between CD28-negative Tem and costimulation blockade-resistant rejection. These results suggest that in some settings, transient T cell-poor chimerism is not sufficient to induce tolerance to a concurrently placed renal allograft and that the presence of this chimerism per se is not an independent biomarker to identify tolerance.","publication_date":"2012,7,1","publication_name":"American Journal of Transplantation","grobid_abstract_attachment_id":"118967109"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Evidence for Kidney Rejection After Combined Bone Marrow and Renal Transplantation Despite Ongoing Whole-Blood Chimerism in Rhesus Macaques","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [44516105]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; 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Patients and methods: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. Results: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. 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href="https://www.academia.edu/7600105/CD154_Blockade_for_Induction_of_Mixed_Chimerism_and_Prolonged_Renal_Allograft_Survival_in_Nonhuman_Primates"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="49669006" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/49669006/Effect_of_ex_vivo_Expanded_Recipient_Regulatory_T_Cells_on_Hematopoietic_Chimerism_and_Kidney_Allograft_Tolerance_Across_MHC_Barriers_in_Cynomolgus_Macaques">Effect of ex vivo Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42315405" href="https://independent.academia.edu/ChengShieWuu">Cheng-Shie Wuu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Transplantation, 2016</p><p class="ds-related-work--abstract ds2-5-body-sm">Infusion of recipient regulatory T cells (Treg) promotes durable mixed hematopoietic chimerism and allograft tolerance in mice receiving allogeneic BMT with minimal conditioning. We applied this strategy in a Cynomolgus macaque model. CD4+CD25high Treg that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and MHC-mismatched BMT with or without Treg infusion. Renal transplantation (from the same BMT donor) was performed 4 months post-BMT without immunosuppression to assess for robust donor-specific tolerance. Transient mixed chimerism, without significant T cell chimerism, was achieved in the animals that received BMT without Treg (N=3). In contrast, the 2 of 5 recipients of Treg + BMT that were evaluable displayed chimerism in all lineages, including T cells, for up to 335 days post-BMT. Importantly, in the animal that survived long-term, &gt;90% of donor T cells were...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effect of ex vivo Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques","attachmentId":67956808,"attachmentType":"pdf","work_url":"https://www.academia.edu/49669006/Effect_of_ex_vivo_Expanded_Recipient_Regulatory_T_Cells_on_Hematopoietic_Chimerism_and_Kidney_Allograft_Tolerance_Across_MHC_Barriers_in_Cynomolgus_Macaques","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/49669006/Effect_of_ex_vivo_Expanded_Recipient_Regulatory_T_Cells_on_Hematopoietic_Chimerism_and_Kidney_Allograft_Tolerance_Across_MHC_Barriers_in_Cynomolgus_Macaques"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="65125229" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/65125229/Induced_regulatory_T_cells_in_allograft_tolerance_via_transient_mixed_chimerism">Induced regulatory T cells in allograft tolerance via transient mixed chimerism</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35122748" href="https://independent.academia.edu/ColvinRobert">Robert Colvin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">JCI insight, 2016</p><p class="ds-related-work--abstract ds2-5-body-sm">Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen. After DBMT, mixed lymphocyte culture with CFSE consistently revealed donor-specific loss of CD8(+) T cell responses in tolerant (TOL) recipients, while marked CD4(+) T cell proliferation in response to donor antigens was found to persist. Interestingly, a significant proportion of the proliferated CD4(+) cells were FOXP3(+) in TOL recipients, but not in AR or naive NHPs...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Induced regulatory T cells in allograft tolerance via transient mixed chimerism","attachmentId":76852840,"attachmentType":"pdf","work_url":"https://www.academia.edu/65125229/Induced_regulatory_T_cells_in_allograft_tolerance_via_transient_mixed_chimerism","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/65125229/Induced_regulatory_T_cells_in_allograft_tolerance_via_transient_mixed_chimerism"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="9442360" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/9442360/CHIMERISM_AND_DONOR_SPECIFIC_NONREACTIVITY_27_TO_29_YEARS_AFTER_KIDNEY_ALLOTRANSPLANTATION">CHIMERISM AND DONOR-SPECIFIC NONREACTIVITY 27 TO 29 YEARS AFTER KIDNEY ALLOTRANSPLANTATION</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="22001203" href="https://independent.academia.edu/HectorRamos5">Hector Ramos</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Transplantation, 1993</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"CHIMERISM AND DONOR-SPECIFIC NONREACTIVITY 27 TO 29 YEARS AFTER KIDNEY ALLOTRANSPLANTATION","attachmentId":47778484,"attachmentType":"pdf","work_url":"https://www.academia.edu/9442360/CHIMERISM_AND_DONOR_SPECIFIC_NONREACTIVITY_27_TO_29_YEARS_AFTER_KIDNEY_ALLOTRANSPLANTATION","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/9442360/CHIMERISM_AND_DONOR_SPECIFIC_NONREACTIVITY_27_TO_29_YEARS_AFTER_KIDNEY_ALLOTRANSPLANTATION"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="78446701" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/78446701/Transient_Mixed_Chimerism_Lymphocyte_Recovery_and_Evidence_for_Early_Donor_Specific_Unresponsiveness_in_Patients_Receiving_Combined_Kidney_and_Bone_Marrow_Transplantation_to_Induce_Tolerance">Transient Mixed Chimerism, Lymphocyte Recovery and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving Combined Kidney and Bone Marrow Transplantation to Induce Tolerance</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42738623" href="https://independent.academia.edu/MeganSykes">Megan Sykes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Transplantation Journal, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline 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href="https://www.academia.edu/78446701/Transient_Mixed_Chimerism_Lymphocyte_Recovery_and_Evidence_for_Early_Donor_Specific_Unresponsiveness_in_Patients_Receiving_Combined_Kidney_and_Bone_Marrow_Transplantation_to_Induce_Tolerance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="63552985" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/63552985/Immune_monitoring_of_transplant_patients_in_transient_mixed_chimerism_tolerance_trials">Immune monitoring of transplant patients in transient mixed chimerism tolerance trials</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42738623" href="https://independent.academia.edu/MeganSykes">Megan Sykes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Human Immunology</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Immune monitoring of transplant patients in transient mixed chimerism tolerance trials","attachmentId":75945753,"attachmentType":"pdf","work_url":"https://www.academia.edu/63552985/Immune_monitoring_of_transplant_patients_in_transient_mixed_chimerism_tolerance_trials","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" 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ds2-5-body-xs">Trends in Immunology, 2017</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mechanisms of Mixed Chimerism-Based Transplant Tolerance","attachmentId":117629925,"attachmentType":"pdf","work_url":"https://www.academia.edu/123120031/Mechanisms_of_Mixed_Chimerism_Based_Transplant_Tolerance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/123120031/Mechanisms_of_Mixed_Chimerism_Based_Transplant_Tolerance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="21668403" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/21668403/T_cell_requirements_for_the_rejection_of_renal_allografts_bearing_an_isolated_class_I_MHC_disparity">T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42822210" href="https://independent.academia.edu/AlastairGracie">Alastair Gracie</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Experimental Medicine</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity","attachmentId":42340188,"attachmentType":"pdf","work_url":"https://www.academia.edu/21668403/T_cell_requirements_for_the_rejection_of_renal_allografts_bearing_an_isolated_class_I_MHC_disparity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/21668403/T_cell_requirements_for_the_rejection_of_renal_allografts_bearing_an_isolated_class_I_MHC_disparity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="3" data-entity-id="33670833" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33670833/Murine_Renal_Allografts_Spontaneous_Acceptance_Is_Associated_with_Regulated_T_Cell_Mediated_Immunity">Murine Renal Allografts: Spontaneous Acceptance Is Associated with Regulated T Cell-Mediated Immunity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="65918729" href="https://independent.academia.edu/PelletierRonald">Ronald Pelletier</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of Immunology, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Murine Renal Allografts: Spontaneous Acceptance Is Associated with Regulated T Cell-Mediated Immunity","attachmentId":53676936,"attachmentType":"pdf","work_url":"https://www.academia.edu/33670833/Murine_Renal_Allografts_Spontaneous_Acceptance_Is_Associated_with_Regulated_T_Cell_Mediated_Immunity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/33670833/Murine_Renal_Allografts_Spontaneous_Acceptance_Is_Associated_with_Regulated_T_Cell_Mediated_Immunity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="4" data-entity-id="59665776" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/59665776/Clinical_experience_with_mixed_chimerism_to_induce_transplantation_tolerance">Clinical experience with mixed chimerism to induce transplantation tolerance</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42738623" href="https://independent.academia.edu/MeganSykes">Megan Sykes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Transplant International, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Clinical experience with mixed chimerism to induce transplantation tolerance","attachmentId":73471664,"attachmentType":"pdf","work_url":"https://www.academia.edu/59665776/Clinical_experience_with_mixed_chimerism_to_induce_transplantation_tolerance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/59665776/Clinical_experience_with_mixed_chimerism_to_induce_transplantation_tolerance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="5" data-entity-id="85396072" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/85396072/Combined_Kidney_and_Bone_Marrow_Transplantation_for_Induction_of_Mixed_Chimerism_and_Renal_Allograft_Tolerance_in_Hla_Mismatched_Transplantation">Combined Kidney and Bone Marrow Transplantation for Induction of Mixed Chimerism and Renal Allograft Tolerance in Hla Mismatched Transplantation</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39490987" href="https://independent.academia.edu/WinfredWilliams">Winfred Williams</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Transplantation Journal, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Combined Kidney and Bone Marrow Transplantation for Induction of Mixed Chimerism and Renal Allograft Tolerance in Hla Mismatched 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