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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4150-4156. Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-04-1629. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1629v1 104/13/4150    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Baev, D. V. Articles by Metelitsa, L. S. Search for Related Content PubMed PubMed Citation Articles by Baev, D. V. Articles by Metelitsa, L. S. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Distinct homeostatic requirements of CD4+ and CD4- subsets of V24-invariant natural killer T cells in humans Denis V. Baev, Xiao-hui Peng, Liping Song, Jerry R. Barnhart, Gay M. Crooks, Kenneth I. Weinberg, and Leonid S. Metelitsa From the Division of Hematology-Oncology, Department of Pediatrics; Division of Research Immunology and Bone Marrow Transplantation, Department of Molecular Microbiology and Immunology, Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA. CD1d-restricted V24-invariant natural killer T cells (iNKTs) are important in immunoregulation. CD4+ and CD4- iNKTs develop with similar frequencies in murine thymus and depend on interleukin-15 (IL-15) in periphery. However, homeostatic requirements of iNKTs have not been analyzed in humans. We evaluated thymic production, peripheral dynamics, and functional maturation of human iNKTs. CD4+ subset comprises 90% of iNKTs in mature thymocytes and cord blood (CB) but only 40% in adult blood. Using T-cell receptor excision circle (TREC) analysis, we directly measured in vivo replicative history of CD4+ and CD4- iNKT cells. Compared to CD4+, CD4- iNKTs contain fewer TRECs, express higher levels of IL-2R, and proliferate with higher rate in response to IL-15. In contrast, CD4+ cells express higher levels of IL-7R and better respond to IL-7. Neither thymic nor CB iNKTs are able to produce cytokines unless they are induced to proliferate. Therefore, unlike in the mouse, human CD4+ iNKTs are mainly supported by thymic output and limited peripheral expansion, whereas CD4- cells undergo extensive peripheral expansion, and both subsets develop their functions in periphery. These findings reveal important differences in homeostatic requirements and functional maturation between murine and human iNKTs that are to be considered for clinical purposes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Bricard, V. Cesson, E. Devevre, H. Bouzourene, C. Barbey, N. Rufer, J. S. Im, P. M. Alves, O. Martinet, N. Halkic, et al. Enrichment of Human CD4+ V{alpha}24/V{beta}11 Invariant NKT Cells in Intrahepatic Malignant Tumors J. Immunol., April 15, 2009; 182(8): 5140 - 5151. [Abstract] [Full Text] [PDF] J. Giustiniani, A. Bensussan, and A. Marie-Cardine Identification and Characterization of a Transmembrane Isoform of CD160 (CD160-TM), a Unique Activating Receptor Selectively Expressed upon Human NK Cell Activation J. Immunol., January 1, 2009; 182(1): 63 - 71. [Abstract] [Full Text] [PDF] M. Moreno, J. W. Molling, S. von Mensdorff-Pouilly, R. H. M. Verheijen, E. Hooijberg, D. 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