Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity
- PMID: 10836360
- DOI: 10.1097/00007890-200004270-00005
Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity
Abstract
Background: Previous studies showed the feasibility of inducing transplantation tolerance to cadaveric renal allografts in patients given pretransplant total lymphoid irradiation (TLI). Microchimerism has been theorized to be an important or necessary factor in long-term graft acceptance and tolerance in humans.
Methods: A cadaveric renal transplant recipient given pretransplant total lymphoid irradiation and withdrawn from immunosuppressive drugs more than 12 years ago was tested for microchimerism using a sensitive nested polymerase chain reaction technique, and for anti-donor reactivity using the mixed leukocyte reaction and an ELISA screen for anti-HLA antibodies. Donor and recipient were mismatched for all HLA-A, B, and DR antigens.
Results: The "tolerant" recipient had good graft function, no detectable donor-type cells in the blood by polymerase chain reaction analysis, vigorous reactivity to donor stimulator cells in the mixed leukocyte reaction, and no detectable serum anti-HLA antibodies.
Conclusions: Operational tolerance to HLA-A, B, and DR mismatched organ allografts can be induced prospectively in humans for at least 12 years after withdrawal of immunosuppressive drugs. The allograft can be maintained in the absence of detectable donor microchimerism and in the presence of anti-donor reactivity in the mixed leukocyte reaction, suggesting that neither chimerism nor clonal deletion or anergy of recipient T cells to alloantigens presented by donor Class II HLA molecules is required for persistence of the tolerant state using this total lymphoid irradiation protocol.
Similar articles
-
Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation.Transplantation. 2002 May 15;73(9):1386-91. doi: 10.1097/00007890-200205150-00005. Transplantation. 2002. PMID: 12023614
-
Prospective study of microchimerism in renal allograft recipients: association between HLA-DR matching, microchimerism and acute rejection.Clin Transplant. 2001 Jun;15(3):192-8. doi: 10.1034/j.1399-0012.2001.150308.x. Clin Transplant. 2001. PMID: 11389710
-
The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.J Clin Invest. 1997 Mar 1;99(5):1118-29. doi: 10.1172/JCI119240. J Clin Invest. 1997. PMID: 9062371 Free PMC article.
-
Donor-specific transfusion and donor bone marrow infusion in renal transplantation tolerance: a review of efficacy and mechanisms.Am J Kidney Dis. 1995 Nov;26(5):701-15. doi: 10.1016/0272-6386(95)90432-8. Am J Kidney Dis. 1995. PMID: 7485121 Review.
-
Chimerism and tolerance: past, present and future strategies to prolong renal allograft survival.Curr Opin Nephrol Hypertens. 2021 Jan;30(1):63-74. doi: 10.1097/MNH.0000000000000666. Curr Opin Nephrol Hypertens. 2021. PMID: 33186221 Review.
Cited by
-
Cell therapeutic approaches to immunosuppression after clinical kidney transplantation.Pediatr Nephrol. 2018 Feb;33(2):199-213. doi: 10.1007/s00467-017-3599-2. Epub 2017 Feb 23. Pediatr Nephrol. 2018. PMID: 28229281 Review.
-
Development of tolerogenic strategies in the clinic.Philos Trans R Soc Lond B Biol Sci. 2005 Sep 29;360(1461):1739-46. doi: 10.1098/rstb.2005.1705. Philos Trans R Soc Lond B Biol Sci. 2005. PMID: 16147538 Free PMC article. Review.
-
Path to clinical transplantation tolerance and prevention of graft-versus-host disease.Immunol Res. 2014 May;58(2-3):240-8. doi: 10.1007/s12026-014-8502-7. Immunol Res. 2014. PMID: 24671802 Free PMC article. Review.
-
Operational tolerance in kidney transplantation and associated biomarkers.Clin Exp Immunol. 2017 Aug;189(2):138-157. doi: 10.1111/cei.12981. Epub 2017 May 29. Clin Exp Immunol. 2017. PMID: 28449211 Free PMC article. Review.
-
Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance.Curr Opin Organ Transplant. 2015 Feb;20(1):49-56. doi: 10.1097/MOT.0000000000000159. Curr Opin Organ Transplant. 2015. PMID: 25563992 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials