Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression.
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http://dx.doi.org/10.1046/j.1600-6143.2003.00320.x | DOI Listing |
Transpl Int
January 2025
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department for General and Visceral Surgery, Berlin, Germany.
Kidney transplantation is the treatment of choice for end-stage organ failure. To improve transplantation outcomes, particularly of "marginal" organs from extended criteria donors (ECD), attempts have been made to therapeutically modulate donor or graft pre-transplantation. Anti-thymocyte globulin (ATG) has a history as lymphocyte-depleting, immunosuppressive drug for treating rejection episodes post transplantation.
View Article and Find Full Text PDFHum Immunol
January 2025
Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address:
With over 30,000 patients having received CAR T cells as a treatment for malignancy, our experience in oncology has facilitated numerous efforts to adapt the CAR therapeutic platform for diseases and conditions beyond cancer. Recognition of their efficacy, where traditional small molecule or biologic therapies fail, has spurred multiple efforts leveraging CAR T cells for immune modulation in the setting of organ/tissue transplantation. In the present review, we discuss CAR T cell approaches that are currently under development, to target both humoral and cellular alloimmunity.
View Article and Find Full Text PDFEur Surg Res
November 2024
Department of Surgery, University of Cambridge, Cambridge, UK.
Background: Normothermic machine perfusion (NMP) is gradually being introduced into clinical transplantation to improve the quality of organs and increase utilisation. This review details current understanding of the underlying mechanistic effects of NMP in the heart, lung, liver, and kidney. It also considers recent advancements to extend the perfusion interval in these organs and the use of NMP to introduce novel therapeutic interventions, with a focus on organ modulation.
View Article and Find Full Text PDFJ Leukoc Biol
November 2024
Chemokine Research Group, School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Sir Graeme Davis Building, 120 University Place, Glasgow G12 8TA, United Kingdom.
Chemokines regulate leukocyte navigation to inflamed sites and specific tissue locales and may therefore be useful for ensuring accurate homing of cell therapeutic products. We, and others, have shown that atypical chemokine receptor 2 (ACKR2)-deficient mice (ACKR2-/-) are protected from metastasis development in cell line and spontaneous mouse models. We have shown that this relates to enhanced CCR2 expression on ACKR2-/- natural killer cells, allowing them to home more effectively to CCR2 ligand-expressing metastatic deposits.
View Article and Find Full Text PDFAnn Hematol
September 2024
Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie Prefecture, Japan.
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