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Blood. 2014 Jul 24;124(4):628-37. doi: 10.1182/blood-2013-12-547349. Epub 2014 May 22.

Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy.

Author information

1
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany; Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, Technische Universität München, Munich, Germany;
2
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany;
3
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany;
4
Clinical Cooperation Group "Immune Monitoring," and.
5
Clinical Cooperation Group "Antigen-specific Immunotherapy," Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany; Institute for Virology, Technische Universität München and Helmholtz Zentrum München, Munich, Germany;
6
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany; Clinical Cooperation Group "Antigen-specific Immunotherapy," Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany;
7
Department of Internal Medicine II, University of Würzburg, Würzburg, Germany;
8
Clinic of Paediatric Oncology, Haematology and Clinical Immunology, Centre for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;
9
Paediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht (Wilhelmina Children´s Hospital), Utrecht, The Netherlands;
10
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Dresden, Germany; Institute of Immunology, Medical Faculty, Dresden University of Technology, Dresden and Center for Regenerative Therapies Dresden, Dresden, Germany;
11
Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service, Johann Wolfgang Goethe University, Frankfurt, Germany;
12
Stage Cell Therapeutics, Göttingen, Germany; and.
13
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany; Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, Technische Universität München, Munich, Germany; Clinical Cooperation Group "Immune Monitoring," and Clinical Cooperation Group "Antigen-specific Immunotherapy," Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany; German Center for Infection Research, Munich, Germany.
14
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany; Clinical Cooperation Group "Immune Monitoring," and Clinical Cooperation Group "Antigen-specific Immunotherapy," Helmholtz Center Munich (Neuherberg) and Technische Universität München, Munich, Germany; German Center for Infection Research, Munich, Germany.

Abstract

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols. To establish a lower limit for successful adoptive T-cell therapy, we conducted low-dose CD8(+) T-cell transfers in the well-established murine Listeria monocytogenes (L.m.) infection model. Major histocompatibility complex-Streptamer-enriched antigen-specific CD62L(hi) but not CD62L(lo) CD8(+) memory T cells proliferated, differentiated, and protected against L.m. infections after prophylactic application. Even progenies derived from a single CD62L(hi) L.m.-specific CD8(+) T cell could be protective against bacterial challenge. In analogy, low-dose transfers of Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients led to strong pathogen-specific T-cell expansion in a compassionate-use setting. In summary, low-dose adoptive T-cell transfer (ACT) could be a promising strategy, particularly for prophylactic treatment of infectious complications after allo-HSCT.

PMID:
24855206
DOI:
10.1182/blood-2013-12-547349
[Indexed for MEDLINE]
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