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Microchimerism, dendritic cell progenitors and transplantation tolerance
1Pittsburgh Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Stem Cells (Dayton, Ohio)
|November 1, 1995
Summary
Donor dendritic cells (DCs) play a crucial role in inducing transplantation tolerance by migrating to lymphoid tissues and downregulating immune responses. These findings highlight DCs
Area of Science:
- Immunology
- Transplantation Biology
- Cellular and Molecular Medicine
Background:
- Multilineage donor leukocyte microchimerism is observed in organ transplant recipients long after transplantation, suggesting donor stem cell survival.
- Donor-derived dendritic cells (DCs) are prominent leukocytes in chimeric graft recipients and are implicated in immune modulation.
- The liver is highly capable of inducing tolerance, and DCs are key players in this process, exhibiting both antigen-presenting and tolerogenic properties.
Purpose of the Study:
- To investigate the role of dendritic cell (DC) progenitors in acquired transplantation tolerance.
- To determine if DC progenitors from liver allografts exhibit tolerogenic properties and contribute to long-term graft survival.
- To explore the potential of donor-derived DCs in inducing alloantigen-specific hyporesponsiveness.
Main Methods:
- Propagation of DC progenitors from mouse liver in response to GM-CSF.
- Analysis of DC progenitor phenotype, including MHC class II and B7 costimulatory molecule expression.
- In vitro studies assessing the activation of naive allogeneic T cells by DC progenitors.
- In vivo studies involving the injection of DC progenitors into allogeneic recipients and monitoring of graft survival.
Main Results:
- Liver-derived DC progenitors express low levels of MHC class II and minimal costimulatory molecules, failing to activate naive allogeneic T cells.
- Injected DC progenitors migrate to lymphoid tissues, upregulate MHC class II, persist indefinitely, and can be propagated from tolerant recipients.
- Bone marrow-derived DC progenitors induce alloantigen-specific hyporesponsiveness (anergy) in vitro and prolong allograft survival in vivo.
Conclusions:
- Bidirectional leukocyte migration and donor cell chimerism, particularly involving DCs, are critical for acquired transplantation tolerance.
- Donor-derived DC progenitors possess tolerogenic properties that can induce alloantigen-specific hyporesponsiveness and prolong allograft survival.
- Understanding the regulation of DC phenotype and function is key to balancing immunogenicity and tolerogenicity in organ transplantation.