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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-06-1833. This Article Full Text (PDF) All Versions of this Article: 2002-06-1833v1 102/2/740    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Billiau, A. D Articles by Waer, M. Search for Related Content PubMed PubMed Citation Articles by Billiau, A. D Articles by Waer, M. Social Bookmarking                   What's this? Submitted June 21, 2002 Accepted March 10, 2003 Transient expansion of Mac1+ Ly6-G+ Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras. Possible implications for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions An D Billiau, Sabine Fevery, Omer Rutgeerts, Willy Landuyt, and Mark Waer* Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium Laboratory of Experimental Radiobiology, University of Leuven, Leuven, Belgium * Corresponding author; email: mark.waer{at}med.kuleuven.ac.be. A murine model of miHCag-mismatched bone marrow transplantation (BMT) was used to study the development of immunoregulatory cells in the posttransplant period and their possible involvement in the dissociated graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactivity of posttransplant donor lymphocyte infusions (DLIs). DLI, applied immediately after BMT, induced GVH disease (GVHD), but when DLI was delayed for 3 weeks, GVHD was avoided while a distinct GVL response was allowed to develop. A population of Mac-1+Ly-6G+Ly-6C+ immature myeloid cells, found in small numbers in normal mice, strongly expanded in spleens of chimeras, reaching a maximum level at week 3 and returning to base level by week 12. Upon isolation, these cells exhibited IFN--dependent, NO-mediated suppressor activity towards in vitro alloresponses, suggesting that, after in vivo DLI, they are activated by IFN- to produce NO and suppress GVH reactivity. As not only alloactivated T cell proliferation, but also leukemia cell-growth was found susceptible to inhibition by exogenous NO, in vivo activation of these cells after DLI may explain the occurrence of a GVL effect despite suppression of GVHD. This suggested sequence of events was supported by the finding that the ex vivo anti-host proliferative response of spleen cells, recovered shortly after in vivo DLI, was characterized by strong mRNA production of the monokines IL-1, IL-6, TNF- and of iNOS. Our data suggest that transiently expanding Mac-1+Ly-6G+Ly-6C+ immature myeloid cells (probably as a result of extramedullary myelopoiesis) may play a role in controlling GVH while promoting GVL reactivity of DLI after allogeneic BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Chakraverty, B. Flutter, F. Fallah-Arani, H.-S. Eom, T. Means, G. Andreola, S. Schwarte, J. Buchli, P. Cotter, G. Zhao, et al. The Host Environment Regulates the Function of CD8+ Graft-versus-Host-Reactive Effector Cells J. Immunol., November 15, 2008; 181(10): 6820 - 6828. [Abstract] [Full Text] [PDF] D. M. Heithoff, E. Y. Enioutina, D. Bareyan, R. A. Daynes, and M. J. Mahan Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity Infect. Immun., November 1, 2008; 76(11): 5191 - 5199. [Abstract] [Full Text] [PDF] G. Gowing, T. Philips, B. Van Wijmeersch, J.-N. Audet, M. 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