Heterologous cells cooperate to augment stem cell migration, homing, and engraftment

  • Gregor B. Adams
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Karissa T. Chabner
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Russell B. Foxall
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Kathryn W. Weibrecht
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Neil P. Rodrigues
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • David Dombkowski
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Robert Fallon
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • Mark C. Poznansky
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.
  • David T. Scadden
    From the Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston; and Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis.

この論文をさがす

説明

<jats:title>Abstract</jats:title> <jats:p>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 β2-microglobulin–deficient nonobese diabetic/severe combined immunodeficiency (β2m−/− 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 or alter endothelial barrier integrity; rather, they affected phosphotyrosine-mediated signaling in CD34+ cells in response to the chemokine stromal derived factor-1α (SDF-1α). 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.</jats:p>

収録刊行物

  • Blood

    Blood 101 (1), 45-51, 2003-01-01

    American Society of Hematology

被引用文献 (1)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ