Differences between graft-versus-leukemia and graft-versus-host reactivity.
I. Interaction of donor immune T cells with tumor and/or host cells
M Rocha, V Umansky, KH Lee, HJ Hacker, A Benner and V Schirrmacher
Deutsches Krebsforschungszentrum Heidelberg, Abteilung Zellulare
Immunologie, FSP Tumorimmunologie, Germany.
Graft-versus-leukemia (GVL) and Graft-versus-host (GVH) reactions were
compared after systemic transfer of allogeneic antitumor immune T
lymphocytes from B10.D2 (H-2d; Mls(b)) into DBA/2 (H-2d; Mis(a)) mice.
Before immune cell transfer, recipient DBA/2 mice were sublethally
irradiated with 5 Gy to prevent host-versus-graft reactivity. Recipients
were either bearing syngeneic metastatic ESb lymphomas (GVL system) or were
normal, non-tumor-bearing mice (GVH system). We previously reported that
this adoptive immunotherapy protocol (ADI) had pronounced GVL activity and
led to immune rejection of even advanced metastasized cancer. In this
study, monoclonal antibodies were used for immunohistochemical analysis of
native frozen tissue sections from either spleen or liver to distinguish
donor from host cells, to differentiate between CD4 and CD8 T lymphocytes,
and to stain sialoadhesin-positive macrophages at different time points
after cell transfer. The kinetics of donor cell infiltration in spleen and
liver differed in that the lymphoid organ was infiltrated earlier (days 1
to 5 after transfer) than the nonlymphoid organ (days 5 to 20). After
reaching a peak, donor cell infiltration decreased gradually and was not
detectable in the spleen after day 20 and in the liver after day 30. The
organ-infiltrating donor immune cells were mostly T lymphocytes and stained
positive for CD4 or CD8 T-cell markers. A remarkable GVL- associated
observation was made with regard to a subset of macrophages bearing the
adhesion molecule sialoadhesin (SER+ macrophages). In the livers of
tumor-bearing mice, their numbers increased between days 1 and 12 after ADI
by a factor greater than 30. Double-staining for donor cell marker and SER
showed that the sialoadhesin-expressing macrophages were of host origin.
The SER+ host macrophages from GVL livers were isolated by enzyme perfusion
and rosetting 12 days after ADI, when they reached peak values of about 60
cells per liver lobule, and were tested, without further antigen addition,
for their capacity to stimulate an antitumor CD8 T-cell response. The
results of this immunologic analysis suggest that these cells in the liver
function as scavengers of the destroyed metastases and as
antigen-processing and - presenting cells for antitumor immune T cells.
Volume 89,
Issue 6,
pp. 2189-2202,
03/15/1997
Copyright © 1997 by The American Society of Hematology
