Article ; Online: In situ activation and expansion of host tregs: a new approach to enhance donor chimerism and stable engraftment in major histocompatibility complex-matched allogeneic hematopoietic cell transplantation.
2009 Volume 15, Issue 7, Page(s) 785–794
Abstract: Host antidonor effector T cells represent a major barrier to the successful engraftment of allogeneic donor hematopoietic progenitor and stem cells. Here, administration of a complex of IL-2 and anti-IL 2 antibodies (IAC) significantly enhanced donor ... ...
Abstract | Host antidonor effector T cells represent a major barrier to the successful engraftment of allogeneic donor hematopoietic progenitor and stem cells. Here, administration of a complex of IL-2 and anti-IL 2 antibodies (IAC) significantly enhanced donor chimerism early as well as long-term engraftment following reduced-intensity conditioning (RIC) and allogeneic major histocompatibility complex (MHC)-matched hematopoietic cell transplantion (HCT). Timing of administration of this complex was crucial: administration of IAC post-HCT more efficiently facilitated marrow engraftment than pre-HCT treatment. Donor chimerism persisted to >6 months post-HCT. Importantly, this approach clearly suppressed the emergence of host antidonor CD8 T cells 2 to 3 weeks post-HCT as assessed by tetramer staining. Following in vivo reactivation of IAC-treated and control recipients at >5 months post-HCT with donor antigen, only PBS-treated control marrow allograft recipients responded with tetramer-binding CD8 cells. In total, the present findings support the notion that the transient activation and expansion of host Tregs in situ post-HCT can be explored as a new approach to regulate host alloreactivity posttransplant. Interestingly, direct stimulation of recipient Treg cells in RIC recipients obviated a requirement for exogenous Treg cell transfusion in this model and may represent a viable alternative to, and/or complement the adaptive transfer of Treg populations in clinical HCT. |
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MeSH term(s) | Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; CD8-Positive T-Lymphocytes/immunology ; Graft Survival/drug effects ; Graft Survival/immunology ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Antigens/immunology ; Host vs Graft Reaction/drug effects ; Host vs Graft Reaction/immunology ; Interleukin-2/immunology ; Interleukin-2/pharmacology ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Mice ; T-Lymphocytes, Regulatory/immunology ; Time Factors ; Transplantation Chimera/immunology ; Transplantation, Homologous |
Chemical Substances | Antibodies, Monoclonal ; Histocompatibility Antigens ; Interleukin-2 |
Language | English |
Publishing date | 2009-05-07 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 1474865-4 |
ISSN | 1523-6536 ; 1083-8791 |
ISSN (online) | 1523-6536 |
ISSN | 1083-8791 |
DOI | 10.1016/j.bbmt.2009.03.011 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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