Document Detail


Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia.
MedLine Citation:
PMID:  19414745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In allogeneic hemopoietic stem cell transplantation, mature donor alphabeta T cells in the allograft promote T cell reconstitution in the recipient and mediate the graft-vs-leukemia (GVL) effect. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-vs-host disease (GVHD). It has previously been shown that effector memory T cells not primed to alloantigen do not cause GVHD yet transfer functional T cell memory and mediate GVL. Recently, central memory T cells (T(CM)) have also been reported to not cause GVHD. In contrast, in this study, we demonstrate that purified CD8(+) T(CM) not specifically primed to alloantigens mediate GVHD in the MHC-mismatched C57BL/6 (B6)-->BALB/c and the MHC-matched, multiple minor histocompatibility Ag-mismatched C3H.SW-->B6 strain pairings. CD8(+) T(CM) and naive T cells (T(N)) caused similar histological disease in liver, skin, and bowel. B6 CD8(+) T(CM) and T(N) similarly expanded in BALB/c recipients, and the majority of their progeny produced IFN-gamma upon restimulation. However, in both models, CD8(+) T(CM) induced milder clinical GVHD than did CD8(+) T(N). Nonetheless, CD8(+) T(CM) and T(N) were similarly potent mediators of GVL against a mouse model of chronic-phase chronic myelogenous leukemia. Thus, in contrast to what was previously thought, CD8(+) T(CM) are capable of inducing GVHD and are substantially different from T(EM) but only subtly so from T(N).
Authors:
Hong Zheng; Catherine Matte-Martone; Dhanpat Jain; Jennifer McNiff; Warren D Shlomchik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  182     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-05-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5938-48     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Transplantation / immunology*
CD8-Positive T-Lymphocytes / immunology*
Disease Models, Animal
Flow Cytometry
Fluorescent Antibody Technique
Graft vs Host Disease / immunology*
Humans
Immunologic Memory
Leukemia, Experimental / immunology*,  therapy
Mice
T-Lymphocyte Subsets / immunology*
Grant Support
ID/Acronym/Agency:
R01-CA96943/CA/NCI NIH HHS; R01-HL 066279/HL/NHLBI NIH HHS

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