|
|
Blood, 15 December 2005, Vol. 106, No. 13, pp. 4397-4406.
Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-05-1775.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation
Katia Perruccio,
Antonella Tosti,
Emanuela Burchielli,
Fabiana Topini,
Loredana Ruggeri,
Alessandra Carotti,
Marusca Capanni,
Elena Urbani,
Antonella Mancusi,
Franco Aversa,
Massimo F. Martelli,
Luigina Romani, and
Andrea Velardi
From the Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine and the Division of Microbiology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Aspergillus and cytomegalovirus are major causes of morbidity/mortality after haploidentical hematopoietic transplantation. The high degree of mismatching makes cell immunotherapy impossible as it would result in lethal graft-versus-host disease (GvHD). We generated large numbers of donor T-cell clones specific for Aspergillus or cytomegalovirus antigens. We identified clones potentially responsible for causing GvHD by screening them for cross-reactivity against recipient mononuclear cells. Nonrecipient reactive, pathogen-specific clones were infused soon after transplantation. They were CD4+ and produced high levels of interferon- and low levels of interleukin-10. In 46 control transplant recipients who did not receive adoptive therapy, spontaneous pathogen-specific T cells occurred in low frequency 9 to 12 months after transplantation and displayed a nonprotective low interferon-/high interleukin-10 production phenotype. In the 35 recipients who received adoptive therapy, one single infusion of donor alloantigen-deleted, pathogen-specific clones in the dose range of 105 to 106 cells/kg body weight did not cause GvHD and induced high-frequency T-cell responses to pathogens, which exhibited a protective high interferon-/low interleukin-10 production phenotype within 3 weeks of infusion. Frequencies of pathogen-specific T cells remained stable over time, and were associated with control of Aspergillus and cytomegalovirus antigenemia and infectious mortality. This study opens new perspectives for reducing infectious mortality after haploidentical transplantations.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
T-cell therapy for viral and fungal infections
- Hermann Einsele
Blood 2005 106: 4023.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Rivera, N. Collins, M. T. Stephan, L. Lipuma, I. Leiner, and E. G. Pamer
Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice
J. Immunol.,
July 1, 2009;
183(1):
631 - 641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dodero, C. Carniti, A. Raganato, A. Vendramin, L. Farina, F. Spina, C. Carlo-Stella, S. Di Terlizzi, M. Milanesi, P. Longoni, et al.
Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery
Blood,
May 7, 2009;
113(19):
4771 - 4779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bozza, R. Gaziano, P. Bonifazi, T. Zelante, L. Pitzurra, C. Montagnoli, S. Moretti, R. Castronari, P. Sinibaldi, G. Rasi, et al.
Thymosin {alpha}1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo
Int. Immunol.,
November 1, 2007;
19(11):
1261 - 1270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Hohl and M. Feldmesser
Aspergillus fumigatus: Principles of Pathogenesis and Host Defense
Eukaryot. Cell,
November 1, 2007;
6(11):
1953 - 1963.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bozza, F. Bistoni, R. Gaziano, L. Pitzurra, T. Zelante, P. Bonifazi, K. Perruccio, S. Bellocchio, M. Neri, A. M. Iorio, et al.
Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation
Blood,
November 15, 2006;
108(10):
3387 - 3396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Romani, F. Bistoni, K. Perruccio, C. Montagnoli, R. Gaziano, S. Bozza, P. Bonifazi, G. Bistoni, G. Rasi, A. Velardi, et al.
Thymosin {alpha}1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance
Blood,
October 1, 2006;
108(7):
2265 - 2274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Beck, M. S. Topp, U. Koehl, E. Roilides, M. Simitsopoulou, M. Hanisch, J. Sarfati, J. P. Latge, T. Klingebiel, H. Einsele, et al.
Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus
Blood,
March 15, 2006;
107(6):
2562 - 2569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
