Journal article

Functional CD47/signal regulatory protein alpha (SIRP alpha) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Nicolas Legrand, Nicholas D Huntington, Maho Nagasawa, Arjen Q Bakker, Remko Schotte, Helene Strick-Marchand, Sandra J de Geus, Stephan M Pouw, Martino Bohne, Arie Voordouw, Kees Weijer, James P Di Santo, Hergen Spits

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2011


The homeostatic control mechanisms regulating human leukocyte numbers are poorly understood. Here, we assessed the role of phagocytes in this process using human immune system (HIS) BALB/c Rag2(-/-)IL-2Rγc(-/-) mice in which human leukocytes are generated from transplanted hematopoietic progenitor cells. Interactions between signal regulatory protein alpha (SIRPα; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of macrophages and other phagocytic cells. We previously showed that B cells develop and survive robustly in HIS mice, whereas T and natural killer (NK) cells survive poorly. Because human CD47 does not interact with BALB/c m..

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Awarded by Dutch Cancer Society

Funding Acknowledgements

We thank Dr. Timo van den Berg and Dr. Mireille Centlivre for their valuable suggestions, Berend Hooibrink for expert maintenance of the flow cytometry platform, the Bloemenhove Clinic (Heemstede, The Netherlands) for providing fetal tissues, and the staff of the Animal Research Institute Amsterdam for animal care. This work was supported by grants from the Bill and Melinda Gates Foundation (Grand Challenges in Global Health Program GC4), Wijnand M. Pon Foundation, College de France, Fondation pour la Recherche Medicale (FRM), Institut Pasteur, and Institut National de la Sante et de la Recherche Medicale (INSERM). N.D.H. was supported by the Human Frontiers Science Program, and R. S. was supported by Dutch Cancer Society Grant NKI 2006-3530.