Document Detail


Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations.
MedLine Citation:
PMID:  9921808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: T cells present in an allogeneic bone marrow transplant may produce graft-versus-host disease but also contribute to immune reconstitution and enhance engraftment. Our aim was to separate alloreactive from nonalloreactive T lymphocytes, by performing a mixed lymphocyte culture (MLC) stimulation of donor cells, followed by selective depletion of activated cells expressing the high-affinity interleukin 2 receptor. We then characterized the resulting depleted cell fraction. METHODS: Donor peripheral blood mononuclear cells were cocultured with irradiated peripheral blood mononuclear cells from HLA-nonidentical recipient stimulators in an MLC. After 3 days, CD25+ lymphocytes (alloreactive cells expressing the alpha chain of the interleukin 2 receptor) were removed by immunomagnetic separation. The depleted donor fraction and untreated cells were then rechallenged in a secondary MLC with the original irradiated stimulator cells or a third party to assess relative alloreactivity. RESULTS: Inhibition of the secondary MLC and of host-specific cytotoxic activities was observed as well as a disappearance of interleukin 2 receptor-positive cells. Alloreactivity against unrelated third-party cells was preserved. Limiting dilution analysis of residual alloantigen-reactive T lymphocytes demonstrated a 1.3 log reduction of antihost reactivity. The depletion largely removed host-specific alloreactive CD4+ cells. CONCLUSIONS: This method reduces alloreactivity while retaining reactivity against third-party targets. This approach may allow therapeutic infusion of T cells after HLA-nonidentical allografts with a reduced capacity to produce graft-versus-host disease.
Authors:
L Garderet; V Snell; D Przepiorka; T Schenk; J G Lu; F Marini; E Gluckman; M Andreeff; R E Champlin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Transplantation     Volume:  67     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-22     Completed Date:  1999-02-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  124-30     Citation Subset:  IM    
Affiliation:
Department of Molecular Hematology and Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030-4095, USA.
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MeSH Terms
Descriptor/Qualifier:
Blood Component Removal*
Coculture Techniques
Humans
Isoantigens / analysis*
Lymphocyte Culture Test, Mixed
Monocytes / physiology*
Phenotype
Receptors, Interleukin-2 / analysis*
T-Lymphocytes / immunology*
T-Lymphocytes, Cytotoxic / physiology
Grant Support
ID/Acronym/Agency:
CA 16672/CA/NCI NIH HHS; P01 CA 49639/CA/NCI NIH HHS; P01 CA 55164/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Isoantigens; 0/Receptors, Interleukin-2

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