Mixed chimerism established by hematopoietic stem cell transplantation is maintained by host and donor T regulatory cells
| Autor: | Luke Maggs, Y. L. Tracey Chan, Hayden Pearce, Paul Moss, Suzy Eldershaw, Jianmin Zuo, Charles F Craddock, Michael J. Griffiths, Jane Nunnick, Charlotte F. Inman, Sandeep Nagra, Ram Malladi, Francesca A M Kinsella |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Hematopoietic stem cell transplantation Biology Chimerism T-Lymphocytes Regulatory B7-H1 Antigen 03 medical and health sciences Graft vs Host Reaction 0302 clinical medicine Immune system In vivo medicine Immune Tolerance Humans Cytotoxicity Transplantation Mixed chimerism Effector Hematopoietic Stem Cell Transplantation Hematology Dendritic Cells In vitro Tissue Donors 030104 developmental biology Immunology Transplantation Tolerance 030215 immunology |
| Popis: | Transplantation is an effective treatment of many clinical disorders, but the mechanisms that regulate immunological tolerance are uncertain and remain central to improving patient outcome. Hemopoietic stem cell transplantation (SCT) often establishes “mixed chimerism” in which immune cells from both the donor and patient coexist in vivo in a setting of immunological tolerance. We studied immune function in 69 patients within 2 months following SCT; 37 were fully donor and 32 displayed mixed chimerism. The proportion of T regulatory (Treg) cells was increased during mixed chimerism and comprised equal numbers of donor and host-derived regulatory cells. This was associated with a tolerogenic PD-L1+ profile on dendritic cells. Importantly, effector T cells from patients with mixed chimerism exhibited reduced cytotoxicity against host target cells in vitro, but this was restored following depletion of CD4+ Treg cells. These data show that Treg cells play a major role in sustaining immunological tolerance during mixed chimerism. These insights should help to guide novel interventions to improve clinical transplantation. |
| Databáze: | OpenAIRE |
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