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.
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.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Shraga
S
Aviner
Xin
X
Yao
Rita
R
Krauthgamer
Yehudit
Y
Gan
Rinat
R
Goren-Arbel
Tirza
T
Klein
Antonio
A
Tabilio
John D
JD
McMannis
Richard
R
Champlin
Massimo F
MF
Martelli
Esther
E
Bachar-Lustig
Yair
Y
Reisner
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002999:Clone Cells; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014019:Tissue Donors