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Specific tolerance induction of allo-K(b)-skin grafts by FK506 in the CD8-depleted H-2(k) recipients required low amounts of K(b)-antigen.
- Source :
-
Transplant immunology [Transpl Immunol] 2005 Oct; Vol. 15 (1), pp. 9-16. - Publication Year :
- 2005
-
Abstract
- MHC class I allo-grafts can be directly rejected by recipient CD8 T cells and be indirectly rejected by recipient CD4 T cells. Although the experimental results using the bm mutant and C57BL/6 mice indicated that CD4-mediated rejection of class I-disparate grafts is a relatively weak process and is expected to be more sensitive to additional exogenous immunosuppression, it is unclear that whether this mechanism can be used for inducing a specific tolerance of class I disparate grafts. In this study, we hypothesize that a short course of FK506 may induce a specific tolerance of class I-disparate skin grafts in the CD8-depleted recipients. K(b)-transgenic C3H mice, Tg.H-2 K(b)-1 and Tg.H-2 K(b)-2 mice that express high copies and low copies of K(b)-antigen respectively were used as donors. Wild type C3H mice (H-2(k)) in which either CD4 or CD8 T cells were depleted by administration of anti-CD4 or CD8 monoclonal antibody (mAb) were used as recipients. Results showed that FK506 promoted longer survival of allo-K(b) skin grafts in CD8-depleted C3H mice than in CD4-depleted C3H mice. Graft survival from Tg.H-2 K(b)-2 mice was significantly longer than Tg.H-2 K(b)-1 mice. A short course of FK506 induced long-term survival of skin grafts from Tg.H-2K(b)-2 mice, but not from Tg.H-2K(b)-1 mice in CD8-depleted C3H recipients, even after FK506 was stopped. These mice also accepted grafts of Tg.H-2K(b)-1 mice when challenged with skin grafts from Tg.H-2K(b)-1 mice, but promptly rejected third party skin grafts from BALB/c (H-2(d)) mice. T cells from K(b)-tolerant C3H mice did not respond to allo-K(b)-antigen in in vitro assays of mixed lymphocyte culture and cell-mediated cytotoxicity. In conclusion we found that a short course of FK506 treatment and low amounts of K(b)-antigen induced a K(b)-specific tolerance in the CD8-depleted recipients, and this tolerance maintained even after withdrawing the anti-CD8 mAb treatment.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes drug effects
Graft Survival immunology
H-2 Antigens genetics
Histocompatibility Antigens Class I immunology
Lymphocyte Depletion
Male
Mice
Mice, Transgenic
CD8-Positive T-Lymphocytes immunology
Graft Survival drug effects
H-2 Antigens immunology
Immunosuppressive Agents pharmacology
Skin Transplantation immunology
Tacrolimus pharmacology
Transplantation Tolerance
Subjects
Details
- Language :
- English
- ISSN :
- 0966-3274
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Transplant immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16223668
- Full Text :
- https://doi.org/10.1016/j.trim.2005.02.005