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 language | English |
|---|---|
| Pages (from-to) | 785-794 |
| Number of pages | 10 |
| Journal | Biology of Blood and Marrow Transplantation |
| Volume | 15 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2009 |
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Keywords
- Allogeneic HCT
- Chimerism
- Engraftment
- MHC-matched
- Tolerance
- Tregs
ASJC Scopus subject areas
- Transplantation
- Hematology
Cite this
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. / Shatry, Alwi; Levy, Robert B.
In: Biology of Blood and Marrow Transplantation, Vol. 15, No. 7, 01.07.2009, p. 785-794.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In Situ Activation and Expansion of Host Tregs
T2 - A New Approach to Enhance Donor Chimerism and Stable Engraftment in Major Histocompatibility Complex-Matched Allogeneic Hematopoietic Cell Transplantation
AU - Shatry, Alwi
AU - Levy, Robert B
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - Allogeneic HCT
KW - Chimerism
KW - Engraftment
KW - MHC-matched
KW - Tolerance
KW - Tregs
UR - http://www.scopus.com/inward/record.url?scp=67349115219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349115219&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2009.03.011
DO - 10.1016/j.bbmt.2009.03.011
M3 - Article
C2 - 19539209
AN - SCOPUS:67349115219
VL - 15
SP - 785
EP - 794
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 7
ER -