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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0353. This Article Full Text (PDF) All Versions of this Article: 2001-12-0353v1 100/2/375    most recent Alert me when this article is cited Alert me if a correction is posted 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 Guimond, M. Articles by Roy, D. C. Search for Related Content PubMed PubMed Citation Articles by Guimond, M. Articles by Roy, D. C. Social Bookmarking                   What's this? Submitted December 28, 2001 Accepted March 13, 2002 P-glycoprotein targeting: a unique strategy to selectively eliminate immunoreactive T cells Martin Guimond, Antonia Balassy, Melanie Barrette, Sylvie Brochu, Claude Perreault, and Denis Claude Roy* * Corresponding author; email: denis-claude.roy{at}umontreal.ca. T lymphocytes have been found to harbor P-glycoprotein (Pgp) and to demonstrate modulation of its ion channel transporter function according to the state of activation of T lymphocytes. We hypothesized that cytotoxic chemicals that are extruded by Pgp could be used to specifically eliminate immunoreactive T cell populations. In this study, we evaluated the capacity of 4,5-dibromorhodamine methyl ester (TH9402), a photosensitizer structurally similar to rhodamine, a dye transported by Pgp, and which becomes highly cytotoxic upon activation with visible light to selectively deplete alloreactive T lymphocytes. Stimulation of T cells with mitogens or allogeneic major histocompatibility complex mismatched cells resulted in the preferential retention of the TH9402 rhodamine-derivative in activated T cells, both CD4+ and CD8+. Photodynamic cell therapy of TH9402-exposed T cells lead to the selective elimination of immunoreactive T cell populations. In addition, this treatment preserved resting T cells and their capacity to respond to third party cells. Inhibition of Pgp enhanced cellular trapping of the dye in non-activated T cells and resulted in their depletion after exposure to light. Targeting of Pgp-deficient cells may therefore represent an appealing strategy for the prevention and treatment of graft-versus-host disease, and other allo- or auto-immune disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. van de Ven, R. Oerlemans, J. W. van der Heijden, G. L. Scheffer, T. D. de Gruijl, G. 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