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

Alwi Shatry, Robert B. Levy

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume15
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • Allogeneic HCT
  • Chimerism
  • Engraftment
  • MHC-matched
  • Tolerance
  • Tregs

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this