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The role of non-deletional tolerance mechanisms in a murine model of mixed chimerism with costimulation blockade.
- Source :
-
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2005 Jun; Vol. 5 (6), pp. 1237-47. - Publication Year :
- 2005
-
Abstract
- Peripheral and central clonal deletion are important tolerance mechanisms in models using bone marrow transplantation (BMT) with costimulation blockade (CB). However, since tolerance can be found before peripheral deletion is complete and since elimination of recipient CD4(+) cells at the time of BMT prevents tolerance induction, we investigated the potential roles of regulation and anergy in such a murine model. We found that transient elimination of CD25(+) cells or neutralization of IL2 immediately after BMT and CB prevented the induction of skin graft tolerance. Cotransfer into SCID mice of CD4(+) cells taken from chimeras early after BMT, together with naive recipient-type CD4(+) cells significantly prolonged donor skin graft survival. In contrast, cotransfer of CD4(+) cells harvested from chimeras late after BMT did not prolong donor skin graft survival. Besides, depletion of CD25(+) cells in established chimeras several months post-BMT did not break tolerance. In vivo administration of recombinant IL2 inhibited chimerism and tolerance neither early nor late post-BMT, arguing against a decisive role for classical anergy. Thus, CD4 cell-mediated regulation contributes significantly to tolerance induction early after BMT, but appears to have no critical role in the maintenance of tolerance.
- Subjects :
- Animals
Antibodies, Monoclonal administration & dosage
CD4-Positive T-Lymphocytes immunology
CD40 Ligand immunology
Female
Graft Rejection immunology
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, SCID
Skin Transplantation immunology
Bone Marrow Transplantation immunology
CD40 Ligand physiology
Clonal Deletion immunology
Graft Survival immunology
Immune Tolerance physiology
Interleukin-2 antagonists & inhibitors
Transplantation Chimera immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1600-6135
- Volume :
- 5
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Publication Type :
- Academic Journal
- Accession number :
- 15888027
- Full Text :
- https://doi.org/10.1111/j.1600-6143.2005.00862.x