|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3550-3557
Depletion of Alloreactive T Cells by a Specific Anti-Interleukin-2
Receptor p55 Chain Immunotoxin Does Not Impair In
Vitro Antileukemia and Antiviral Activity
Daniela Montagna,
Eric Yvon,
Valeria Calcaterra,
Patrizia Comoli,
Franco Locatelli,
Rita Maccario,
Alain Fisher, and
Marina Cavazzana-Calvo
From the Laboratorio di Immunologia e Unità di Trapianto di
Midollo Osseo, Dipartimento di Scienze Pediatriche, Università
degli Studi di Pavia, IRCCS Policlinico San Matteo, Pavia, Italy; and
E.T.S and INSERM Unité 429, Hôpital Necker-Enfant Malades,
Paris, France.
The success of bone marrow transplantation (BMT) from HLA-disparate
donors depends on the development of new strategies able, on one hand,
to efficiently prevent graft-versus-host disease (GVHD) and, on the
other hand, to protect leukemic patients from relapse and infections.
Using an immunotoxin (IT) directed against the  chain (p55) of the
human interleukin-2 receptor (RFT5-SMPT-dgA), we previously showed that
it is possible to kill mature T cells activated against a specific HLA
complex by a one-way mixed lymphocyte culture (MLC). The present study
was performed to investigate whether this protocol of allodepletion
affects the capacity of residual T cells to display antileukemia and
antiviral activity evaluated by limiting dilution assays (LDA),
measuring the frequency of cytotoxic T-lymphocyte precursors (CTLp)
directed against autologous leukemic blasts (LB) and cytomegalovirus
(CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia
activity was evaluated in peripheral blood mononuclear cells (PBMC) of
3 patients treated for acute myeloid leukemia who had developed a high
frequency of LB-reactive CTLp after either autologous or allogeneic
BMT. Results demonstrate that (1) depletion with RFT5-SMPT-dgA
efficiently inhibited MLC; (2) fresh PBMC of patients yielded a high
frequency of LB-reactive CTLp comparable to that of the mock-treated
PBMC; and (3) effector cells obtained after allodepletion fully
retained the capacity to lyse pretransplant LB. By contrast, the
frequency of CTLp directed against patient's pretransplant BM
remission cells was always undetectable. Data obtained in 4 healthy
donors showed that specifically allodepleted T cells recognized and
killed autologous CMV-infected fibroblasts and autologous
EBV-B-lymphoblastoid cell lines. In conclusion, our data indicate that
allodepletion using RFT5-SMPT-dgA efficiently removed alloreactive
cells, while sparing in vitro antileukemic and antiviral cytotoxic responses.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
A. M. LEEN, G. D. MYERS, C. M. BOLLARD, M. H. HULS, U. SILI, A. P. GEE, H. E. HESLOP, and C. M. ROONEY
T-Cell Immunotherapy for Adenoviral Infections of Stem-Cell Transplant Recipients
Ann. N.Y. Acad. Sci.,
December 1, 2005;
1062(1):
104 - 115.
[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]
|
|
|
|
|
|
|
D. Watson, G. Y. Zhang, M. Sartor, and S. I. Alexander
"Pruning" of Alloreactive CD4+ T Cells Using 5- (and 6-)Carboxyfluorescein Diacetate Succinimidyl Ester Prolongs Skin Allograft Survival
J. Immunol.,
December 1, 2004;
173(11):
6574 - 6582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Farag
Depletion of alloreactive T cells: which cell?
Blood,
December 1, 2004;
104(12):
3422 - 3423.
[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]
|
|
|
|
|
|
|
B. J. Chen, X. Cui, G. D. Sempowski, C. Liu, and N. J. Chao
Transfer of allogeneic CD62L- memory T cells without graft-versus-host disease
Blood,
February 15, 2004;
103(4):
1534 - 1541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-J. Kolb, C. Schmid, A. J. Barrett, and D. J. Schendel
Graft-versus-leukemia reactions in allogeneic chimeras
Blood,
February 1, 2004;
103(3):
767 - 776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Godfrey, M. R. Krampf, P. A. Taylor, and B. R. Blazar
Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation
Blood,
February 1, 2004;
103(3):
1158 - 1165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Amrolia, G. Muccioli-Casadei, E. Yvon, H. Huls, U. Sili, E. D. Wieder, C. Bollard, J. Michalek, V. Ghetie, H. E. Heslop, et al.
Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses
Blood,
September 15, 2003;
102(6):
2292 - 2299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Michalek, R. H. Collins, H. P. Durrani, P. Vaclavkova, L. E. Ruff, D. C. Douek, and E. S. Vitetta
Definitive separation of graft-versus-leukemia- and graft-versus-host-specific CD4+ T cells by virtue of their receptor beta loci sequences
PNAS,
February 4, 2003;
100(3):
1180 - 1184.
[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]
|
|
|
|
|
|
|
M. Guimond, A. Balassy, M. Barrette, S. Brochu, C. Perreault, and D. C. Roy
P-glycoprotein targeting: a unique strategy to selectively eliminate immunoreactive T cells
Blood,
June 28, 2002;
100(2):
375 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Chen, X. Cui, C. Liu, and N. J. Chao
Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging process
Blood,
May 1, 2002;
99(9):
3083 - 3088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. F. Hartwig, M. Robbers, C. Wickenhauser, and C. Huber
Murine acute graft-versus-host disease can be prevented by depletion of alloreactive T lymphocytes using activation-induced cell death
Blood,
April 15, 2002;
99(8):
3041 - 3049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Montagna, R. Maccario, F. Locatelli, V. Rosti, Y. Yang, P. Farness, A. Moretta, P. Comoli, E. Montini, and A. Vitiello
Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy
Blood,
December 1, 2001;
98(12):
3359 - 3366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. d. C. Bittencourt, S. Perruche, E. Contassot, S. Fresnay, M.-H. Baron, R. Angonin, F. Aubin, P. Herve, P. Tiberghien, and P. Saas
Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers
Blood,
July 1, 2001;
98(1):
224 - 230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Handgretinger, P. Lang, M. Schumm, M. Pfeiffer, S. Gottschling, B. Demirdelen, P. Bader, S. Kuci, T. Klingebiel, and D. Niethammer
Immunological Aspects of Haploidentical Stem Cell Transplantation in Children
Ann. N.Y. Acad. Sci.,
June 1, 2001;
938(1):
340 - 358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Volpi, K. Perruccio, A. Tosti, M. Capanni, L. Ruggeri, S. Posati, F. Aversa, A. Tabilio, L. Romani, M. F. Martelli, et al.
Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants
Blood,
April 15, 2001;
97(8):
2514 - 2521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Obst, N. Netuschil, K. Klopfer, S. Stevanovi, and H.-G. Rammensee
The Role of Peptides in T Cell Alloreactivity Is Determined by Self-Major Histocompatibility Complex Molecules
J. Exp. Med.,
March 6, 2000;
191(5):
805 - 812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W Lowdell and M. B C Koh
Immunotherapy of AML: future directions
J. Clin. Pathol.,
January 1, 2000;
53(1):
49 - 54.
[Full Text]
[PDF]
|
|
|
| |
