The difficulty of eliminating donor leukocyte microchimerism in rat recipients bearing established organ allografts

Tetsuma Kiyomoto, Hideyoshi Toyokawa, Atsunori Nakao, Takashi Kaizu, Anthony J. Demetris, Thomas E. Starzl, Noriko Murase

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background. Unequivocal eradication of donor leukocyte microchimerism from recipients of long-surviving organ transplants has never been reported. Here we describe a drastic attempt to accomplish this objective. Methods. In control experiments, a rank order of microchimerism and of associated donor specific nonreactivity was produced in Brown-Norway (BN) rats by transplantation of Lewis (LEW) liver, bone marrow cell (BMC) and heart allografts under a brief course of tacrolimus. The degree of microchimerism at 60 and 110 days was estimated with semiquanitative immunocytochemical and PCR techniques. Tolerance at 110 days was assessed in the different control groups by challenge transplantation of naïve LEW hearts. In parallel experimental groups, an attempt was made to eliminate microchimerism from the BN recipients. The animals were submitted at 60 days to 9.5-Gy total body irradiation (TBI), reconstituted immediately with naïve BN BMC, and tested for donor specific nonreactivity by LEW heart transplantation at 110 days. Results. After the TBI-reconstitution at 60 days, microchimerism was undetectable in BMC recipients at 110 days, significantly reduced in heart recipients, and least affected in liver recipients. Except in liver recipients, abrogation of LEW-specific nonreactivity was demonstrated by rejection of the priming grafts, or by rejection of the challenge heart grafts, and by in vitro immune assay. Conclusions. It is difficult to eliminate microchimerism in organ recipients once the donor cells have settled into tissue niches.

Original languageEnglish
Pages (from-to)438-444
Number of pages7
JournalTransplantation
Volume81
Issue number3
DOIs
Publication statusPublished - Feb 2006
Externally publishedYes

Fingerprint

Chimerism
Allografts
Leukocytes
Bone Marrow Cells
Whole-Body Irradiation
Norway
Transplants
Liver
Graft Rejection
Tacrolimus
Heart Transplantation
Liver Transplantation
Transplantation
Polymerase Chain Reaction
Control Groups

Keywords

  • Bone marrow cells
  • Liver transplantation
  • Microchimerism
  • Passenger leukocytes
  • Tolerance

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

The difficulty of eliminating donor leukocyte microchimerism in rat recipients bearing established organ allografts. / Kiyomoto, Tetsuma; Toyokawa, Hideyoshi; Nakao, Atsunori; Kaizu, Takashi; Demetris, Anthony J.; Starzl, Thomas E.; Murase, Noriko.

In: Transplantation, Vol. 81, No. 3, 02.2006, p. 438-444.

Research output: Contribution to journalArticle

Kiyomoto, Tetsuma ; Toyokawa, Hideyoshi ; Nakao, Atsunori ; Kaizu, Takashi ; Demetris, Anthony J. ; Starzl, Thomas E. ; Murase, Noriko. / The difficulty of eliminating donor leukocyte microchimerism in rat recipients bearing established organ allografts. In: Transplantation. 2006 ; Vol. 81, No. 3. pp. 438-444.
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abstract = "Background. Unequivocal eradication of donor leukocyte microchimerism from recipients of long-surviving organ transplants has never been reported. Here we describe a drastic attempt to accomplish this objective. Methods. In control experiments, a rank order of microchimerism and of associated donor specific nonreactivity was produced in Brown-Norway (BN) rats by transplantation of Lewis (LEW) liver, bone marrow cell (BMC) and heart allografts under a brief course of tacrolimus. The degree of microchimerism at 60 and 110 days was estimated with semiquanitative immunocytochemical and PCR techniques. Tolerance at 110 days was assessed in the different control groups by challenge transplantation of na{\"i}ve LEW hearts. In parallel experimental groups, an attempt was made to eliminate microchimerism from the BN recipients. The animals were submitted at 60 days to 9.5-Gy total body irradiation (TBI), reconstituted immediately with na{\"i}ve BN BMC, and tested for donor specific nonreactivity by LEW heart transplantation at 110 days. Results. After the TBI-reconstitution at 60 days, microchimerism was undetectable in BMC recipients at 110 days, significantly reduced in heart recipients, and least affected in liver recipients. Except in liver recipients, abrogation of LEW-specific nonreactivity was demonstrated by rejection of the priming grafts, or by rejection of the challenge heart grafts, and by in vitro immune assay. Conclusions. It is difficult to eliminate microchimerism in organ recipients once the donor cells have settled into tissue niches.",
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