Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Yi Zhang; Gerard Joe; Jiang Zhu; Richard Carroll; Bruce Levine; Elizabeth Hexner; Carl June; Stephen G. Emerson

doi:10.1182/blood-2003-09-3135

Dendritic cell-activated CD44^hiCD8⁺ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Yi Zhang
, Gerard Joe
, Jiang Zhu
, Richard Carroll
, Bruce Levine
, Elizabeth Hexner
, Carl June
, Stephen G. Emerson

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8⁺ T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44 ^hiCD8⁺ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44^loCD8⁺ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44 ^loCD8⁺ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44^loCD8⁺ T cells, CD44 ^hiCD8⁺ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8⁺ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.

Original language	English
Pages (from-to)	3970-3978
Number of pages	9
Journal	Blood
Volume	103
Issue number	10
DOIs	https://doi.org/10.1182/blood-2003-09-3135
State	Published - May 15 2004

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

Access to Document

10.1182/blood-2003-09-3135

Cite this

@article{45afd0c4e636415f8ea11adc9b2b1e6e,

title = "Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity",

abstract = "Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8+ T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44 hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44 loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44 hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.",

author = "Yi Zhang and Gerard Joe and Jiang Zhu and Richard Carroll and Bruce Levine and Elizabeth Hexner and Carl June and Emerson, \{Stephen G.\}",

year = "2004",

month = may,

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doi = "10.1182/blood-2003-09-3135",

language = "English",

volume = "103",

pages = "3970--3978",

journal = "Blood",

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publisher = "Elsevier B.V.",

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T1 - Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

AU - Zhang, Yi

AU - Joe, Gerard

AU - Zhu, Jiang

AU - Carroll, Richard

AU - Levine, Bruce

AU - Hexner, Elizabeth

AU - June, Carl

AU - Emerson, Stephen G.

PY - 2004/5/15

Y1 - 2004/5/15

N2 - Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8+ T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44 hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44 loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44 hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.

AB - Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8+ T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44 hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44 loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44 hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.

UR - https://www.scopus.com/pages/publications/2342480419

U2 - 10.1182/blood-2003-09-3135

DO - 10.1182/blood-2003-09-3135

M3 - Article

C2 - 14764532

SN - 0006-4971

VL - 103

SP - 3970

EP - 3978

JO - Blood

JF - Blood

IS - 10

ER -