Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Aug 15;76(3):588-96.
doi: 10.1097/01.TP.0000080980.26287.11.

Regulatory cell-mediated tolerance does not protect against chronic rejection

Takaaki Koshiba  1 , Hiroaki Kitade, Boudewijn Van Damme, Annapaula Giulietti, Lut Overbergh, Chantal Mathieu, Mark Waer, Jacques Pirenne
Affiliations

Regulatory cell-mediated tolerance does not protect against chronic rejection

Takaaki Koshiba et al. Transplantation. .

Abstract

Background: Regulatory cells prevent graft loss to acute rejection and induce tolerance, possibly by promoting Th2 deviation. Th2 cytokines stimulate B cells, which cause alloantibody-mediated chronic rejection. We searched to determine whether regulatory cell-mediated tolerance protects or not against chronic rejection.

Methods: Heart transplantation (Htx) was performed using RA (RT1P) and PVG (RT1c) rats as donor and recipients. Donor-specific blood transfusion (DSBT) was given on preTx day 12. Secondary grafts were implanted at day 100. Splenocytes were transferred from tolerant rats (and controls) into lightly irradiated (450 rad) naive PVG, which received RA Htx. Primary Htx were investigated for the development of vascular occlusion (VO), the production of Th1/Th2 intragraft cytokines, and for the nature of graft infiltrate as well as for endothelial deposition of immunoglobulin (Ig)G isotypes and complement (C3) binding. Results were compared with rejecting controls (no DSBT) and syngeneic Htx.

Results: RA Htx were rejected within 10 days (8, 9, 10x4). PreTx DSBT prolonged primary Htx survival indefinitely (>140 days) with acceptance of secondary donor-specific (but not third-party) grafts (P<0.001). Naive irradiated PVG rats given splenocytes from tolerant rats but not from controls accepted RA Htx, showing the existence of regulatory cells in allograft acceptors. Despite being tolerant, DSBT-treated rats displayed typical features of chronic rejection at day 90 (VO=77%; P<0.001 vs. VO=4% in syngeneic rats). An overt Th2 deviation, particularly intragraft production of interleukin (IL)-4, was observed at day 30. Simultaneously to this Th2 deviation, B cells emerged in the grafts and endothelial deposition of IgG1 (Th2 dependent) and C3 binding were observed.

Conclusions: Regulatory cells that prevent graft loss to acute rejection in primary and secondary grafts do not protect against the development of chronic rejection.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Immunoregulatory function of IL-27 and TGF-β1 in cardiac allograft transplantation.
    Le Texier L, Thebault P, Carvalho-Gaspar M, Vignard V, Merieau E, Usal C, Cuturi MC, Wood KJ, Chiffoleau E. Le Texier L, et al. Transplantation. 2012 Aug 15;94(3):226-33. doi: 10.1097/TP.0b013e31825b0c38. Transplantation. 2012. PMID: 22790384 Free PMC article.
  • Regulatory T cells in transplantation.
    Wood KJ. Wood KJ. Transplant Proc. 2011 Jul-Aug;43(6):2135-6. doi: 10.1016/j.transproceed.2011.06.050. Transplant Proc. 2011. PMID: 21839214 Free PMC article. Review.
  • Donor-Specific Blood Transfusion in Lung Transplantation.
    Jin X, Pirenne J, Vos R, Hooft C, Kaes J, Van Slambrouck J, Kortleven P, Vandervelde C, Beeckmans H, Kerckhof P, Carlon MS, Van Raemdonck D, Looney MR, Vanaudenaerde BM, Ceulemans LJ. Jin X, et al. Transpl Int. 2024 Oct 30;37:12822. doi: 10.3389/ti.2024.12822. eCollection 2024. Transpl Int. 2024. PMID: 39553536 Free PMC article. Review.

LinkOut - more resources