Antilymphocytic antibodies and marrow transplantation. VIII. Recipient
conditioning with Clq-affine monoclonal anti-pan T antibodies prevents GVHD
in homozygous fully mismatched mice
S Thierfelder, U Kummer, R Schuh and J Mysliwietz
An approach to suppressing secondary disease with antibodies was studied
that differed from conventional antibody treatment of donor marrow in
vitro. It consisted of the selection of anti-Thy-1 antibodies with high
affinity for Clq, the first subunit of the complement cascade, and a single
injection of such antibodies into prospective irradiated marrow recipients.
Monoclonal mouse IgM and rat IgG 2c antibodies of high titers in
complement-dependent test systems but with low affinity for Clq caused
little immunosuppression. Monoclonal rat IgG2b or mouse IgG2a anti-Thy-1
antibodies with high affinity for Clq prevented acute and chronic mortality
of graft-v-host disease (GVHD), however, when injected in irradiated CBA or
AKR mice prior to C57BL/6 spleen and/or bone marrow cell transfusion. This
treatment simultaneously suppressed residual host-v-graft reactivity of the
irradiated mice, so that permanent hematopoietic engraftment ensued even at
5 or 6 Gy. Full chimerism and specific tolerance were obtained. Primary
immune response to SRBC was clearly depressed in the chimeras; secondary
immune response was not. Clearance of T cell antibody activity (greater
than 6 days), timing, and dose of injected antibody, as well as other
modalities of the conditioning treatment that may have contributed to the
remarkable immunosuppression, are discussed.
Volume 68,
Issue 4,
pp. 818-824,
10/01/1986
Copyright © 1986 by The American Society of Hematology
