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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4375-4386
Sialoadhesin-Positive Host Macrophages Play an Essential Role in
Graft-Versus-Leukemia Reactivity in Mice
Susanne Müerköster,
Marian Rocha,
Paul R. Crocker,
Volker Schirrmacher, and
Victor Umansky
From the Division of Cellular Immunology, Tumor Immunology Program,
German Cancer Research Center, Heidelberg, Germany; and The Wellcome
Trust Building, Department of Biochemistry, University of Dundee,
Dundee, UK.
We recently established an effective immune T-cell-mediated
graft-versus-leukemia (GVL) murine model system in which complete tumor
remissions were achievable even in advanced metastasized cancer. We now
describe that this T-cell-mediated therapy is dependent on host
macrophages expressing the lymphocyte adhesion molecule sialoadhesin
(Sn). Depletion of Kupffer cells in tumor-bearing mice during adoptive
immunotherapy (ADI) or the treatment of these animals with anti-Sn
monoclonal antibodies led to complete or partial inhibition of the
immune T-cell-mediated therapeutic effect. Furthermore,
Sn+ host macrophages in livers formed clusters during ADI
with donor CD8 T cells. To test for a possible antigen presentation
function of these macrophages, we used as an in vitro model the antigen  -galactosidase for which a dominant major histocompatibility complex
(MHC) class I Ld-restricted peptide epitope is
known to be recognized by specific CD8 cytotoxic T lymphocytes (CTL).
We demonstrate that purified Sn+ macrophages can process
exogenous -galactosidase and stimulate MHC class I
peptide-restricted CTL responses. Thus, Sn+ macrophages,
which are significantly increased in the liver after ADI, may process
tumor-derived proteins via the MHC class I pathway as well as via the
MHC class II pathway, as shown previously, and present respective
peptide epitopes to CD8 as well as to CD4 immune T cells, respectively.
The synergistic interactions observed before between immune CD4 and CD8
T cells during ADI could thus occur in the observed clusters with
Sn+ host macrophages.
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