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Blood, 1 July 2006, Vol. 108, No. 1, pp. 238-245. Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2006-01-0190. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2006-01-0190v1 108/1/238    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 Legrand, N. Articles by Spits, H. Search for Related Content PubMed PubMed Citation Articles by Legrand, N. Articles by Spits, H. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2-/-c-/- mice Nicolas Legrand, Tom Cupedo, Anja U. van Lent, Menno J. Ebeli, Kees Weijer, Thomas Hanke, and Hergen Spits From the Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam (AMC-UvA), Amsterdam, the Netherlands; The Netherlands Cancer Institute—Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands; and TeGenero ImmunoTherapeutics AG, Science Park Würzburg, Würzburg, Germany. Efficient and quick reconstitution of T-cell compartments in lymphopenic patients is of great importance to prevent opportunistic infections, but remains difficult to achieve. Human T-cell proliferation in a T-cell-receptor (TCR)-independent manner is possible in vitro with superagonist anti-CD28 antibodies, and such molecules are therefore promising therapeutic tools. Here, we investigated the in vivo effects of superagonist anti-CD28 treatment on human developing and mature T cells, in the recently developed model of "human immune system" BALB/c Rag2-/-c-/- mice. Our results show that superagonist anti-CD28 treatment transiently induces a 7-fold increase in thymocyte numbers and up to 18-fold accumulation of mature thymocytes. The increased thymic production lead to transient accumulation of mature T cells in the periphery at the peak of treatment effect (day 6). In addition, long-term peripheral T-cell depletion was induced. Furthermore, the concomitant selective expansion and accumulation of suppressive CD4+CD25+FoxP3+ T cells was induced in a transient manner. Superagonist anti-CD28 therapy could therefore be of clinical interest in humans, both for beneficial effect on thymic T-cell production as well as regulatory T-cell accumulation. (Blood. 2006;108:238-245) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Rosinol, A. Oriol, M. V. Mateos, A. Sureda, P. Garcia-Sanchez, N. Gutierrez, A. Alegre, J. J. Lahuerta, J. de la Rubia, C. Herrero, et al. Phase II Pethema Trial of Alternating Bortezomib and Dexamethasone As Induction Regimen Before Autologous Stem-Cell Transplantation in Younger Patients With Multiple Myeloma: Efficacy and Clinical Implications of Tumor Response Kinetics J. Clin. Oncol., October 1, 2007; 25(28): 4452 - 4458. [Abstract] [Full Text] [PDF] J. A. Katzel, P. Hari, and D. H. Vesole Multiple Myeloma: Charging Toward a Bright Future CA Cancer J Clin, September 1, 2007; 57(5): 301 - 318. [Abstract] [Full Text] [PDF] V. Mirenda, S. J. Jarmin, R. David, J. Dyson, D. Scott, Y. Gu, R. I. Lechler, K. Okkenhaug, and F. M. Marelli-Berg Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28 Blood, April 1, 2007; 109(7): 2968 - 2977. [Abstract] [Full Text] [PDF] S. Gorantla, H. Sneller, L. Walters, J. G. Sharp, S. J. Pirruccello, J. T. West, C. Wood, S. Dewhurst, H. E. Gendelman, and L. Poluektova Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2-/-{gamma}c-/- Mice J. Virol., March 15, 2007; 81(6): 2700 - 2712. [Abstract] [Full Text] [PDF]

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