Sialoadhesin-positive host macrophages play an essential role in graft-versus-leukemia reactivity in mice

• Verfasst von: Sebens, Susanne [VerfasserIn]
• Verfasst von: Schirrmacher, Volker [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Sialoadhesin-positive host macrophages play an essential role in graft-versus-leukemia reactivity in mice
• Verf.angabe: Susanne Müerköster, Marian Rocha, Paul R. Crocker, Volker Schirrmacher, and Victor Umansky
• E-Jahr: 1999
• Jahr: June 15, 1999
• Umfang: 12 S.
• Fussnoten: Gesehen am 20.02.2019 ; Der Vorname von Viktor Umansky ist in der Vorlage mit "c" geschrieben
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 1999
• Band/Heft Quelle: 93(1999), 12, Seite 4375-4386
• ISSN Quelle: 1528-0020
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1587840987

Abstract

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 β-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 β-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.