Title
Skin allograft maintenance in a new synchimeric model system of tolerance
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Medicine, Division of Diabetes; Department of Pathology
Publication Date
2001-11-21
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Treatment of mice with a single donor-specific transfusion plus a brief course of anti-CD154 mAb uniformly induces donor-specific transplantation tolerance characterized by the deletion of alloreactive CD8+ T cells. Survival of islet allografts in treated mice is permanent, but skin grafts eventually fail unless recipients are thymectomized. To analyze the mechanisms underlying tolerance induction, maintenance, and failure in euthymic mice we created a new analytical system based on allo-TCR-transgenic hemopoietic chimeric graft recipients. Chimeras were CBA (H-2(k)) mice engrafted with small numbers of syngeneic TCR-transgenic KB5 bone marrow cells. These mice subsequently circulated a self-renewing trace population of anti-H-2(b)-alloreactive CD8+ T cells maturing in a normal microenvironment. With this system, we studied the maintenance of H-2(b) allografts in tolerized mice. We documented that alloreactive CD8+ T cells deleted during tolerance induction slowly returned toward pretreatment levels. Skin allograft rejection in this system occurred in the context of 1) increasing numbers of alloreactive CD8+ cells; 2) a decline in anti-CD154 mAb concentration to levels too low to inhibit costimulatory functions; and 3) activation of the alloreactive CD8+ T cells during graft rejection following deliberate depletion of regulatory CD4+ T cells. Rejection of healed-in allografts in tolerized mice appears to be a dynamic process dependent on the level of residual costimulation blockade, CD4+ regulatory cells, and activated alloreactive CD8+ thymic emigrants that have repopulated the periphery after tolerization.
DOI of Published Version
10.4049/jimmunol.167.11.6623
Source
J Immunol. 2001 Dec 1;167(11):6623-30.
Journal/Book/Conference Title
Journal of immunology (Baltimore, Md. : 1950)
Related Resources
PubMed ID
11714833
Repository Citation
Iwakoshi NN, Markees TG, Turgeon NA, Thornley TB, Cuthbert A, Leif J, Phillips NE, Mordes JP, Greiner DL, Rossini AA. (2001). Skin allograft maintenance in a new synchimeric model system of tolerance. GSBS Student Publications. https://doi.org/10.4049/jimmunol.167.11.6623. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/564