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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-09-2712.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3581-3589
IMMUNOBIOLOGY
Modified myeloid dendritic cells act as regulatory dendritic
cells to induce anergic and regulatory T cells
Katsuaki Sato,
Naohide Yamashita,
Masanori Baba, and
Takami Matsuyama
From the Department of Immunology and Medical Zoology,
Division of Human Retroviruses, Center for Chronic Viral Diseases,
School of Medicine, Kagoshima University, Kagoshima City, Kagoshima,
Japan; and the Department of Advanced Medical Science, The
Institute of Medical Science, University of Tokyo,
Japan.
To exploit a novel strategy to regulate T cell-mediated immunity,
we established human and murine modified dendritic cells (DCs) with
potent immunoregulatory properties (designed as regulatory DCs), which
displayed moderately high expression levels of major histocompatibility
complex (MHC) molecules and extremely low levels of costimulatory
molecules compared with their normal counterparts. Unlike human normal
DCs, which caused the activation of allogeneic CD4+ and
CD8+ T cells, human regulatory DCs not only induced their
anergic state but also generated CD4+ or CD8+
regulatory T (Tr) cells from their respective naive subsets in vitro. Although murine normal DCs activated human xenoreactive T cells
in vitro, murine regulatory DCs induced their hyporesponsiveness. Furthermore, transplantation of the primed human T cells
with murine normal DCs into severe combined immunodeficient (SCID) mice
enhanced the lethality caused by xenogeneic graft-versus-host disease
(XGVHD), whereas transplantation of the primed human T cells with
murine regulatory DCs impaired their ability to cause XGVHD. In
addition, a single injection of murine regulatory DCs following
xenogeneic or allogeneic transplantation protected the recipients from
the lethality caused by XGVHD as well as allogeneic acute GVHD. Thus,
the modulation of T cell-mediated immunity by regulatory DCs provides
a novel therapeutic approach for immunopathogenic diseases.
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