Transfusion-related immunomodulation due to peripheral blood dendritic cells expressing the CD200 tolerance signaling
David A Clark1, Reginald M Gorczynski, Morris A Blajchman
1Department of Medicine, Immunology and Inflammation Program, McMaster University, Hamilton, Ontario, Canada.
Background:
The transfusion of allogeneic blood products containing white cells (WBCs) has been reported to reduce resistance to infection, stimulate the growth of some types of tumors in animal models, and prevent abortion of allogeneic embryos in the CBAxDBA/2 murine model.
Study Design And Methods:
In this study, the issue explored was whether allogeneic BALB/c whole blood given to C57Bl/6 mice by tail vein after injection of syngeneic FSL-10 fibrosarcoma cells increased the number of lung nodules enumerated on Day 21. The effect on the tumor growth-promoting effect produced by allogeneic BALB/c whole blood was then examined by exposure of the allogeneic BALB/c blood to various monoclonal antibodies (MoAbs). The antibodies added to the BALB/c blood included anti-murine CD200 antibodies, anti-lymphoid dendritic cell (DC) antibodies (DEC205), or anti-myeloid DC (anti-CD11c) antibodies.
Results:
The tumor growth-promoting effect of the allogeneic BALB/c blood was abrogated by the addition to the BALB/c blood of MoAb either to myeloid DCs (anti-CD11c) or to the CD200 tolerance signaling molecule, but not by adding MoAb to lymphoid DCs (DEC205). BALB/c blood also was shown to increase the percentage of transforming growth factor (TGF)-beta+ splenocytes detected in recipient mice, on Day 12 after transfusion. This effect was abrogated by adding anti-CD200 antibody to the BALB/c donor blood. Moreover, physiologic concentrations of TGF-beta, but not interleukin-10, were shown to stimulate, in cell culture experiments, the proliferation of syngeneic FSL-10 sarcoma cells.
Conclusions:
These data support the hypothesis that the mechanism of the tumor growth-promoting effect of allogeneic blood is mediated by a highly potent population of peripheral blood DCs expressing the CD200 tolerance signaling molecule. These data also indicate that tumor cell growth can be mediated by the stimulation of TGF-beta-producing cells and that TGF-beta may act by tumor cell growth stimulation, rather than by host immunosuppression.
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