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Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor
using cyclosporine-induced syngeneic graft-versus-host disease in the rat
RB Geller, AH Esa, WE Beschorner, CG Frondoza, GW Santos and AD Hess
Johns Hopkins Oncology Center, Baltimore, MD 21205.
Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and
then treated with cyclosporine (CsA) for 40 consecutive days following
transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA
cessation. This model of GVHD was used to define and characterize a
graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell
line which expresses class II major histocompatibility (MHC) antigen (Ia).
Nylon wool-nonadherent spleen cells from animals who developed syngeneic
GVHD were capable of significant lysis against chromium-labeled tumor
target cells in a four- hour chromium released cell mediated lympholysis
assay; maximum lysis occurred five days following cessation of CsA when
clinical signs first appeared. Cytolytic activity declined to baseline as
GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte
subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype
(non-helper T) were capable of significant lysis against tumor target
cells. Lysis of tumor cells was blocked by preincubation with monoclonal
antibodies (MoAb) specific for the rat anti-class II MHC antigen but not
with MoAb against class I. Incubation of tumor cells with gamma-interferon
increased expression of tumor class II MHC antigens and significantly
increased their susceptibility to lysis by nylon wool-nonadherent
splenocytes from animals with syngeneic GVHD. These studies have
demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor;
the effector cell is a CTL of the OX8 phenotype specific for the class II
MHC antigen.
Volume 74,
Issue 3,
pp. 1165-1171,
08/15/1989
Copyright © 1989 by The American Society of Hematology
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