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Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes depleted of graft-versus-host reactivity: a new source for graft facilitating cells in bone marrow transplantation.

Abstract：

:Induction of donor type chimerism in mildly prepared hosts without graft-versus-host disease (GvHD) is a most desirable goal in bone morrow transplantation. We have recently demonstrated in a mouse model that donor veto cytotoxic T lymphocytes (CTLs) can facilitate the induction of donor type chimerism in sublethally irradiated recipients without causing GvHD if they are effectively depleted of alloreactivity against host cells by means of stimulation against a third party. We extend this approach to human cells, by preparing CTLs in two major steps: primary culture in the absence of interleukin 2, leading to death by neglect of antihost clones, and addition of interleukin 2 and subsequent dilution of antihost clones as a consequence of the expansion of the anti-third-party clones. CTLs prepared in this way specifically suppress host cytotoxic T cells directed against antigens of the donor, but not against fourth-party antigens, as demonstrated in a standard (51)Cr release assay. We conclude that human anti-third-party CTLs afford a new source of veto cells that are depleted of potential graft-versus-host-reactive clones. The cells generated by this approach could potentially be used to facilitate engraftment of allogeneic hematopoietic stem cells.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Aviner S,Yao X,Krauthgamer R,Gan Y,Goren-Arbel R,Klein T,Tabilio A,McMannis JD,Champlin R,Martelli MF,Bachar-Lustig E,Reisner Y

doi

10.1016/j.humimm.2005.03.004

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

644-52

issue

6

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(05)00066-2

journal_volume

66

pub_type

杂志文章

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