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Biol Blood Marrow Transplant. 2009 Jul;15(7):785-94. doi: 10.1016/j.bbmt.2009.03.011. Epub 2009 May 7.

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.

Author information

1
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA. ashary@med.miami.edu

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.

PMID:
19539209
PMCID:
PMC2700954
DOI:
10.1016/j.bbmt.2009.03.011
[Indexed for MEDLINE]
Free PMC Article

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