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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3365-3371. Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2003-03-0982. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0982v1 105/8/3365    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 Arditti, F. D. Articles by Reisner, Y. Search for Related Content PubMed PubMed Citation Articles by Arditti, F. D. Articles by Reisner, Y. Related Collections Immunobiology Neoplasia Transplantation Apoptosis Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Eradication of B-CLL by autologous and allogeneic host nonreactive anti–third-party CTLs Fabian D. Arditti, Shraga Aviner, Benjamin Dekel, Rita Krauthgamer, Judith Gan, Arnon Nagler, Antonio Tabilio, Massimo Martelli, Alain Berrebi, and Yair Reisner From the Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; the Hematology Institute, Kaplan Medical Center, Rehovot, Israel; the Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel; and the Department of Hematology, University of Perugia, Perugia, Italy. Establishment of cell lines capable of killing leukemia cells, in the absence of alloreactivity against normal host cells, represents a most desirable goal in bone marrow transplantation (BMT) and cancer immunotherapy. By using a human mouse chimeric model, we demonstrate that allogeneic anti-third-party cytotoxic T lymphocytes (CTLs) depleted of alloreactivity are endowed with a potent anti-B-cell chronic lymphocytic leukemia (B-CLL) reactivity. Likewise, CTL preparations generated from autologous T cells of the same patients with B-CLL exhibited comparable leukemia eradication, suggesting that the reactivity of allogeneic anti-third-party CTLs is not mediated by residual antihost clones. This specificity was also exhibited in vitro, and annexin staining revealed that B-CLL killing is mediated by apoptosis. While the CTLs killing of third-party cells could be blocked by anti-CD3 antibody, the lysis of the B-CLL cells was not inhibited by this antibody, suggesting a T-cell receptor (TCR)-independent cytotoxicity. The role of cell contact leading to apoptosis of B-CLL cells is shown in transwell plates and by anti-lymphocyte function-associated antigen-1 (LFA-1)-blocking antibody. Up-regulation of CD54 and the subsequent apoptosis of B-CLL cells depend on the initial LFA-1/ICAM-1 (intercellular adhesion molecule 1) interaction. Taken together, these results suggest that allogeneic or autologous host nonreactive anti-third-party CTLs may represent a new therapeutic approach for patients with B-CLL. (Blood. 2005;105:3365-3371) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-T. Rubio, T. I. Saito, K. Kattleman, G. Zhao, J. Buchli, and M. Sykes Mechanisms of the Antitumor Responses and Host-versus-Graft Reactions Induced by Recipient Leukocyte Infusions in Mixed Chimeras Prepared with Nonmyeloablative Conditioning: A Critical Role for Recipient CD4+ T Cells and Recipient Leukocyte Infusion-Derived IFN-{gamma}-Producing CD8+ T Cells J. Immunol., July 15, 2005; 175(2): 665 - 676. [Abstract] [Full Text] [PDF]

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