Iyengar, AR and Bonham, CA and Antonysamy, MA and Subbotin, VM and Khanna, A and Murase, N and Rao, AS and Starzl, TE and Thomson, AW
(1997)
Striking augmentation of hematopoietic cell chimerism in noncytoablated allogeneic bone marrow recipients by flt3 ligand and tacrolimus.
Transplantation, 63 (9).
1193 - 1199.
ISSN 0041-1337
Abstract
The influence of granulocyte-macrophage colony-stimulating factor (GM- CSF) and the recently identified hematopoietic stem-progenitor cell mobilizing factor flt3 ligand (FL) on donor leukocyte microchimerism in noncytodepleted recipients of allogeneic bone marrow (BM) was compared. B10 mice (H2b) given 50 x 106 allogeneic (B10.BR [H2(k)]) BM cells also received either GM-CSF (4 μg/day s.c.), FL (10 μg/day i.p.), or no cytokine, with or without concomitant tacrolimus (formerly FK506; 2 mg/kg) from day 0. Chimerism was quantitated in the spleen 7 days after transplantation by both polymerase chain reaction (donor DNA [major histocompatibility complex class II; I-E(k)]) and immunohistochemical (donor [I-E(k+)] cell) analyses. Whereas GM-CSF alone significantly augmented (fivefold) the level of donor DNA in recipients' spleens, FL alone caused a significant (60%) reduction. Donor DNA was increased 10-fold by tacrolimus alone, whereas coadministration of GM-CSF and tacrolimus resulted in a greater than additive effect (28-fold increase). A much more striking effect was observed with FL + tacrolimus (>125-fold increase in donor DNA compared with BM alone). These findings were reflected in the relative numbers of donor major histocompatibility complex class II+ cells (many resembling dendritic cells) detected in spleens, although quantitative differences among the groups were less pronounced. Evaluation of cytotoxic T lymphocyte generation by BM recipients' spleen cells revealed that FL alone augmented antidonor immunity and that this was reversed by tacrolimus. Thus, although FL may potentiate antidonor reactivity in nonimmunosuppressed, allogeneic BM recipients, it exhibits potent chimerism-enhancing activity when coadministered with recipient immunosuppressive therapy. This property of FL may offer considerable potential for the augmentation of microchimerism, with therapeutic implications for organ allograft survival and tolerance induction.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Iyengar, AR | | | | Bonham, CA | | | | Antonysamy, MA | | | | Subbotin, VM | | | | Khanna, A | | | | Murase, N | | | | Rao, AS | | | | Starzl, TE | tes11@pitt.edu | TES11 | | Thomson, AW | | | |
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Centers: |
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute |
Date: |
15 May 1997 |
Date Type: |
Publication |
Journal or Publication Title: |
Transplantation |
Volume: |
63 |
Number: |
9 |
Page Range: |
1193 - 1199 |
DOI or Unique Handle: |
10.1097/00007890-199705150-00001 |
Institution: |
University of Pittsburgh |
Refereed: |
Yes |
ISSN: |
0041-1337 |
Other ID: |
uls-drl:31735062134253, Starzl CV No. 1968 |
Date Deposited: |
08 Apr 2010 17:33 |
Last Modified: |
22 Jun 2021 14:56 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/5354 |
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