Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3968-3975
Graft-Versus-Host Disease and Graft-Versus-Leukemia Effect in Mice
Grafted With Peripheral Newborn Blood
Véronique de La Selle,
Eliane Gluckman, and
Martine Bruley-Rosset
From INSERM Unité 267, Immunogénétique des
Allogreffes, Villejuif, France; and Unité de transplantation de
moelle osseuse, Hôpital Saint-Louis, Paris, France.
We previously used peripheral newborn blood (NBB) as a possible in
vivo experimental model for cord blood (CB) transplantation and showed
that B10.D2 NBB cells successfully reconstituted adult (DBA/2 × B10.D2)F1 mice without causing graft-versus-host disease (GVHD),
probably because of their phenotypic and functional immaturity. Here we
investigated the influence of T-cell maturation occurring in NBB cells
during the early postbirth period on the degree of engraftment, the
incidence of GVHD, and the graft-versus-leukemia (GVL) potential. These
parameters were compared in recipients grafted with bone marrow (BM)
cells. We observed an increased percentage of CD4+ mature
T cells accompanied by the acquisition of proliferative responses to
phytohemagglutinin (PHA) and to allogeneic cells of day-5 NBB cells.
The capacity of day-2 NBB to engraft was moderately reduced and
recipients developing GVHD were occasionally observed after the graft
of day-5 NBB cells. No GVL effect was evidenced regardless of the time
of postbirth blood collection. However, the GVL effect can be obtained
by the delayed infusion of donor mature T cells to recipients grafted
with day-0 NBB, without causing GVHD. In contrast, the same protocol
applied to mice grafted with BM cells induced GVHD mortality of all
recipients. Interleukin (IL)-10 but not IL-2 messenger RNA was
expressed in NBB cells as opposed to BM cells. These findings suggest
that, in terms of GVHD incidence, delayed infusion of mature T cells as
post-transplant tumor immunotherapy would be more effective when
applied after CB than after BM transplantation.
