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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-02-0486. This Article Full Text (PDF) All Versions of this Article: 2002-02-0486v1 101/1/45    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 Adams, G. B Articles by Scadden, D. T Search for Related Content PubMed PubMed Citation Articles by Adams, G. B Articles by Scadden, D. T Social Bookmarking                   What's this? Submitted February 15, 2002 Accepted July 3, 2002 Heterologous cells cooperate to augment stem cell migration, homing and engraftment Gregor B Adams, Karissa T Chabner, Russell B Foxall, Kathryn W Weibrecht, Neil P Rodrigues, David Dombkowski, Robert Fallon, Mark C Poznansky, and David T Scadden* Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA * Corresponding author; email: scadden.david{at}mgh.harvard.edu. T-lymphocyte depletion of bone marrow grafts compromises engraftment, suggesting a facilitating mechanism provided by the T-cells that has been shown to associate with CD8+, but not CD4+ T-cells. Explanations for this phenomenon have focused on immune targeting of residual host cells or cytokine production. We provide evidence for an alternative mechanism based on cooperative effects on cell motility. We observed that engraftment of CD34+ cells in a ß2m-/- NOD/SCID mouse model paralleled clinical observations in humans, with an enhancing effect noted from the addition of CD8+ cells, but not CD4+ cells. This correlated with CD8+ augmentation of CD34+ cell homing to the bone marrow in vivo and CD8+ cell associated increases of CD34+ cell transmigration through a bone marrow endothelial cell line in vitro. The cooperative interaction was not sensitive to brefeldin A inhibition of protein secretion. However, cytochalasin D induced inhibition of CD8+ cytoskeletal rearrangements abrogated CD34+ transendothelial migration and impaired CD34+ cell homing in vivo. CD8+ cells did not migrate in tandem with CD34+ cells nor alter endothelial barrier integrity, rather they affected phosphotyrosine mediated signaling in CD34+ cells in response to the chemokine SDF-1. These data demonstrate cell-cell cooperativity between different cell types in mediating chemotactic events and provide one potential explanation for the clinically observed effect of CD8+ cells on bone marrow transplantation. This modification of cell migration by neighboring cells provides broad possibilities for combinatorial effects between cells of different types to influence cell localization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bridenbaugh, L. Kenins, E. Bouliong-Pillai, C. P. Kalberer, E. Shklovskaya, A. Gratwohl, and A. Wodnar-Filipowicz Clinical stem-cell sources contain CD8+CD3+ T-cell receptor-negative cells that facilitate bone marrow repopulation with hematopoietic stem cells Blood, February 1, 2008; 111(3): 1735 - 1738. [Abstract] [Full Text] [PDF] W. H. Peranteau, M. Endo, O. O. Adibe, A. Merchant, P. W. Zoltick, and A. W. 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