Sialoadhesin-positive host macrophages play an essential role in graft-versus-leukemia reactivity in mice
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 lymph...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 15, 1999
|
| In: |
Blood
Year: 1999, Volume: 93, Issue: 12, Pages: 4375-4386 |
| ISSN: | 1528-0020 |
| Online Access: | Verlag, Volltext: http://www.bloodjournal.org/content/93/12/4375
|
| Author Notes: | Susanne Müerköster, Marian Rocha, Paul R. Crocker, Volker Schirrmacher, and Victor Umansky |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 20.02.2019 Der Vorname von Viktor Umansky ist in der Vorlage mit "c" geschrieben |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |