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

Shraga Aviner, Xin Yao, Rita Krauthgamer, Yehudit Gan, Rinat Goren-Arbel, Tirza Klein, Antonio Tabilio, John D. McMannis, Richard Champlin, Massimo F. Martelli, Esther Bachar-Lustig, Yair Reisner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 51Cr 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.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalHuman Immunology
Volume66
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Cytotoxic lymphocytes
  • GvHD

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this