|
|
Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0353.
 Previous Article | Table of Contents | Next Article 
Blood, 15 July 2002, Vol. 100, No. 2, pp. 375-382
PLENARY PAPER
P-glycoprotein targeting: a unique strategy to selectively
eliminate immunoreactive T cells
Martin Guimond,
Antonia Balassy,
Mélanie Barrette,
Sylvie Brochu,
Claude Perreault, and
Denis
Claude Roy
From the Division of Hematology-Immunology,
Maisonneuve-Rosemont Hospital Research Center, Department of Medicine,
Université de Montréal, and Theratechnologies Inc,
Montreal, QC, Canada.
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 on 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 led 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
nonactivated 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 alloimmune or autoimmune disorders.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al.
A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique
Blood,
April 15, 2008;
111(8):
4392 - 4402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al.
Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
Blood,
September 1, 2007;
110(5):
1689 - 1697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. C. Wehler, M. Nonn, B. Brandt, C. M. Britten, M. Grone, M. Todorova, I. Link, S. A. Khan, R. G. Meyer, C. Huber, et al.
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines
Blood,
January 1, 2007;
109(1):
365 - 373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
Blood,
September 15, 2006;
108(6):
1797 - 1808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Solomon, S. Mielke, B. N. Savani, A. Montero, L. Wisch, R. Childs, N. Hensel, J. Schindler, V. Ghetie, S. F. Leitman, et al.
Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation
Blood,
August 1, 2005;
106(3):
1123 - 1129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. R. Martins, L. S. St. John, R. E. Champlin, E. D. Wieder, J. McMannis, J. J. Molldrem, and K. V. Komanduri
Functional assessment and specific depletion of alloreactive human T cells using flow cytometry
Blood,
December 1, 2004;
104(12):
3429 - 3436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Barrett, K. Rezvani, S. Solomon, A. M. Dickinson, X. N. Wang, G. Stark, H. Cullup, M. Jarvis, P. G. Middleton, and N. Chao
New Developments in Allotransplant Immunology
Hematology,
January 1, 2003;
2003(1):
350 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
