Donor Lymphocyte Infusion-Mediated Graft-versus-Host Responses in a Preclinical Swine Model of Haploidentical Hematopoietic Cell Transplantation.
Biol Blood Marrow Transplant
; 22(11): 1953-1960, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27543159
ABSTRACT
We previously described successful hematopoietic stem cell engraftment across MHC barriers in miniature swine without graft-versus-host disease (GVHD) using novel reduced-intensity conditioning regimens consisting of partial transient recipient T cell-depletion, thymic or low-dose total body irradiation, and a short course of cyclosporine A. Here we report that stable chimeric animals generated with these protocols are strongly resistant to donor leukocyte infusion (DLI)-mediated GVH effects. Of 33 total DLIs in tolerant chimeras at clinical doses, 21 failed to induce conversion to full donor hematopoietic chimerism or cause GVHD. We attempted to overcome this resistance to conversion through several mechanisms, including using sensitized donor lymphocytes, increasing the DLI dose, removing chimeric host peripheral blood cells through extensive recipient leukapheresis before DLI, and using fully mismatched lymphocytes. Despite our attempts, the resistance to conversion in our model was robust, and when conversion was achieved, it was associated with GVHD in most animals. Our studies suggest that delivery of unmodified hematopoietic stem cell doses under reduced-intensity conditioning can induce a potent, GVHD-free, immune tolerant state that is strongly resistant to DLI.
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Base de dados:
MEDLINE
Assunto principal:
Doadores de Sangue
/
Transfusão de Linfócitos
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Transplante Haploidêntico
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Doença Enxerto-Hospedeiro
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article