CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease.

CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Research Abstract Details 

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CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Abstract Text:

Yi Zhang,Elizabeth Hexner,Dale Frank,Stephen G Emerson,

Acute and chronic graft-versus-host disease (GVHD) remain the major complications limiting the efficacy of allogeneic hemopoietic stem cell transplantation. Chronic GVHD can evolve from acute GVHD, or in some cases may overlap with acute GVHD, but how acute GVHD evolves to chronic GVHD is unknown. In this study, in a classical CD8+ T cell-dependent mouse model, we found that pathogenic donor CD4+ T cells developed from engrafted hemopoietic stem cells (HSCs) in C57BL/6SJL(B6/SJL, H-2(b)) mice suffering from acute GVHD after receiving donor CD8+ T cells and HSCs from C3H.SW mice (H-2(b)). These CD4+ T cells were activated, infiltrated into GVHD target tissues, and produced high levels of IFN-gamma. These in vivo-generated CD4+ T cells caused lesions characteristic of chronic GVHD when adoptively transferred into secondary allogeneic recipients and also caused GVHD when administered into autologous C3H.SW recipients. The in vivo generation of pathogenic CD4+ T cells from engrafted donor HSCs was thymopoiesis dependent. Keratinocyte growth factor treatment improved the reconstitution of recipient thymic dendritic cells in CD8+ T cell-repleted allogeneic hemopoietic stem cell transplantation and prevented the development of pathogenic donor CD4+ T cells. These results suggest that de novo-generated donor CD4+ T cells, arising during acute graft-versus-host reactions, are key contributors to the evolution from acute to chronic GVHD. Preventing or limiting thymic damage may directly ameliorate chronic GVHD.

CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Publishing Authors By Initials

Y Zhang,E Hexner,D Frank,SG Emerson,

For similar persons: tissue donors research abstracts see: persons: tissue donors research

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CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 179

Page Numbers: 3305-14

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Sep

YEAR: 2007

CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Keywords Mesh Terms:

KEYWORDS: Tissue Donors

MESH TERMS: immunology

Chemical & Substance for Abstract: CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease. Information

Substance Name: Fibroblast Growth Factor 7

Registry Number: 126469-10-1

Grant and Affiliation Information for CD4+ T cells generated de novo from donor hemopoietic stem cells mediate the evolution from acute to chronic graft-versus-host disease.

AFFILIATION: Department of Medicine and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA 102464-01

ACRONYM: CA

MEDLINETA: J Immunol

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