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Immature rat myeloid dendritic cells generated in low-dose granulocyte macrophage-colony stimulating factor prolong donor-specific rat cardiac allograft survival.
- Source :
-
Transplantation [Transplantation] 2003 Feb 27; Vol. 75 (4), pp. 521-8. - Publication Year :
- 2003
-
Abstract
- Background: Because the differential polarization of T cells in response to antigen presentation is dependent on the maturational state of dendritic cells (DCs), we hypothesized that the adoptive transfer of immature myeloid DCs (iMDCs) would prolong graft survival.<br />Methods: To evaluate this hypothesis, we studied the effects of transfer of iMDCs and mature myeloid DCs (mMDCs) on rat cardiac allograft survival.<br />Results: Whereas iMDCs that do not express costimulatory molecules induce allogeneic T-cell hyporesponsiveness in coculture studies, mMDCs that express high levels of major histocompatibility complex class II costimulatory and maturation molecules induce a robust allostimulatory T-cell response. Adoptive transfer of Wistar Furth iMDCs, unlike mMDCs, 7 days before cardiac transplantation significantly prolonged graft survival. It was important that adoptive transfer of iMDCs combined with 0.5 mL antilymphocyte serum (ALS) transient immunosuppression on day -7 led to donor-specific permanent graft survival in 50% of recipients. In contrast, adoptive transfer of mMDCs combined with ALS led to graft survival similar to that in recipients treated with ALS alone. Stimulation of CD4 T cells isolated from the spleen of unresponsive allograft recipients with donor antigen resulted in donor-specific hyporesponsiveness and production of interleukin (IL)-10 and transforming growth factor-beta but not IL-4 and interferon-gamma. The tolerant T-cell unresponsiveness was reversed by the addition of IL-2.<br />Conclusion: Our data confirming the immunoregulatory effect of immature DCs indicate that induction of transplant tolerance by iMDCs is partly dependent on in vivo generation of regulatory T cells. This finding suggests that immunization with immature donor DCs has therapeutic potential for the induction of transplant tolerance and treatment of autoimmune diseases.
- Subjects :
- Adoptive Transfer
Animals
Biomarkers
Bone Marrow Cells cytology
Bone Marrow Cells drug effects
Cell Differentiation drug effects
Cell Differentiation immunology
Dendritic Cells drug effects
Flow Cytometry
Graft Rejection immunology
Lymphocyte Culture Test, Mixed
Major Histocompatibility Complex immunology
Rats
Rats, Inbred ACI
Rats, Inbred Lew
Rats, Inbred WF
Transplantation, Homologous
Dendritic Cells cytology
Graft Survival immunology
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Heart Transplantation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 75
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 12605121
- Full Text :
- https://doi.org/10.1097/01.TP.0000048380.84355.4A